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This article comes from WeChat WeChat official account:With freehand brushwork biotech (Biotech(ID：TXYBiotech), Author: Yang Yi, original title: "Anti-influenza drugs and market analysis", title map from: vision china.

The ugly SARS-CoV-19 has not been completely conquered by human beings, and the lingering influenza virus has begun to wreak havoc again. The struggle between human beings and viruses is like this."Scientific Progress-Virus Variation and Drug Resistance"It spirals up in this cycle. The periodic spread of seasonal influenza virus makes the importance of anti-influenza drug development stand out again.

Oseltamivir, which went on the market 24 years ago, is still the mainstay of anti-influenza drugs. Although the first new drug, Baloshavir, enriched the team of anti-influenza drugs, it went on the market five years ago. After learning the cruelty of SARS-CoV-19 virus, people need to make a breakthrough in the development of influenza drugs.

I. Classification of seasonal influenza

Seasonal influenza（Seasonal influenza）It is an acute respiratory infectious disease caused by influenza virus prevalent all over the world. There are four types of seasonal influenza viruses, A, B, C and D.(Chinese corresponds to influenza A, B, C and D). Influenza A and B viruses spread and cause seasonal epidemics.（seasonal epidemics）.

According to the hemagglutinin on the surface of the virus（HA， hemagglutinin）And neuraminidase（NA， neuraminidase）The combination of influenza A virus is further divided into different subtypes. At present, subtype A is transmitted among humans.（H1N1）And a（H3N2）Influenza virus. A（H1N1）Influenza virus is also written as A.（H1N1）Pdm09, because it caused a pandemic in 2009, replaced the seasonal influenza A spread before 2009.（H1N1）Viruses.

Only influenza A virus is known to cause a pandemic at present. Influenza B virus is not classified into subtypes, but can be classified into lineages. The currently popular influenza B virus belongs to B/Yamagata or B/Victoria pedigree. The detection frequency of influenza C virus is low, which usually causes mild infection, so it is not of public health importance. Influenza D virus mainly affects cattle and does not infect or cause human diseases.^[1]

Second, influenza treatment

Seasonal flu patients without complications, if they have symptoms, stay at home and do their bit to reduce the spread of the virus. By means of self-monitoring, we can decide whether to seek medical treatment.

Patients suffering from serious or progressive clinical diseases related to influenza, that is, pneumonia, septicemia or clinical syndrome aggravated by chronic basic diseases, should receive antiviral drugs as soon as possible. The most common anti-influenza drugs are neuraminidase inhibitors.（Neuraminidase inhibitors）Oseltamivir（oseltamivir）. Ideally, it should be taken within 48 hours of symptoms to maximize the curative effect. It is recommended to treat for at least 5 days, but it can be extended until the clinical improvement is satisfactory.

It should be noted that corticosteroids should not be used for influenza.(corticosteroid, such as prednisone, cortisone, hydrocortisone, etc.)Unless there are other reasons.(e.g. asthma and other specific conditions)Because corticosteroids may lead to prolonged virus clearance time and double infection of bacteria or fungi caused by immunosuppression.

At present, all popular influenza viruses are resistant to adamantane antiviral drugs.(Adamantane antivirals, such as amantadine and rimantadine)Because of their drug resistance, these drugs are not recommended for monotherapy.^[1]

Third, anti-influenza drugs

The main anti-influenza drugs are divided into adamantane, neuraminidase inhibitors and polymerase inhibitors.(Table 1).^[2]There are four kinds of anti-influenza drugs approved by FDA recommended by the Centers for Disease Control and Prevention: Rapivab. （peramivir），Relenza（zanamivir），Tamiflu （oseltamivir phosphate）And Xofluza（baloxavir marboxil）.^[3]

Table 1. Antiinfluenza drugs

1. Neuraminidase inhibitors（Neuraminidase inhibitors）　

Neuraminidase inhibitor（NAI）Targeted neuraminidase（NA）Glycoprotein, which is second only to hemagglutinin in human body.（HA）The most abundant surface glycoprotein. Neuraminidase inhibitors can achieve antiviral effect by inhibiting the emergence of new virus particles in host cells and preventing the enzyme activity necessary for virus transmission.^[4]

The four most common neuraminidase inhibitors are oseltamivir, zanamivir, peramivir and laninamivir.(Figure 1).

Fig. 1. Common neuraminidase inhibitors and their molecular structures.

Although their structures are similar, there are obvious differences in treatment schemes, routes of administration and drug resistance. The most widely used neuraminidase inhibitor is oseltamivir.(Trade name: Tamiflu)The treatment plan for adults is 75mg twice a day for 5 days. Due to zanamivir(trade name Relenza)The oral bioavailability of is low.（<5%）Therefore, it is approved as an inhalation drug, 5mg each time, twice a day for 5 days.

In 2019, intravenous zanamivir(trade name Dectova)Authorized by the European Union to be used under special circumstances.(e.g. in case of resistance to other anti-influenza drugs). Efforts to increase bioavailability and half-life have led to peramivir.(Trade name: Rapivab/Rapiacta/PeramiFlu)Development of, by intravenous infusion with a single dose of 600mg; And ranimivir (trade name Inavir), a more persistent neuraminidase inhibitor, showed therapeutic effect after a single nasal inhalation dose.^[5] Paramivir and Ranimivir are allowed to be used in a few countries around the world, while oseltamivir and zanamivir are more widely approved geographically.

Different neuraminidase inhibitors show different efficacy, which mainly depends on the subtype/pedigree of influenza virus that infects patients.For example, oseltamivir versus A（H1N1）, a（H3N2）And the seasonal uncomplicated influenza caused by influenza A and B virus is more effective. However, the effect of antiviral therapy may be limited by the resistance of influenza virus to neuraminidase inhibitors. Different neuraminidase inhibitors have different drug resistance.

In view of the drug resistance of common neuraminidase inhibitors, people are now focusing on emerging drugs in research. At least two new neuraminidase inhibitors and one neuraminidase blocker are in the first and second development stages.

HNC042(Guangzhou Hengnuokang Pharmaceutical Technology Co., Ltd. and Heilongjiang Zhenbaodao Pharmaceutical Co., Ltd.)In preclinical studies, it showed effective inhibitory activity against wild-type and oseltamivir-resistant NA-H274Y virus. HNC042 showed good safety, tolerability and linear pharmacokinetics in phase I trials in the United States.Learning (NCT04603989). HNC042 is used to prevent and treat influenza, especially for critically ill patients who need hospitalization.

AV5080(ChemRar, Russia, Viriom, USA, Figure 2)The preclinical evaluation revealed the activity against a variety of influenza viruses, including oseltamivir-resistant strains. Oral AV5080 shows good physicochemical and metabolic characteristics and good pharmacokinetic characteristics in animals.^[6]

Fig. 2. chemical structure of a new neuraminidase inhibitor drug candidate AV5080.

CD388 (Cidora Therapeutics Inc., USA)It is a long-acting neuraminidase blocker, and its structure is obtained by coupling neuraminidase of influenza virus to human antibody fragment.(Fc）Proprietary variants of the domain, so as to achieve two completely different and complementary mechanisms.(Figure 3). This new method of preventing and treating virus infection is expected to provide universal protection throughout the flu season. By targeting highly conserved virus areas, CD388 can potentially protect individuals from all influenza strains, including seasonal and pandemic influenza A, influenza B and major drug-resistant viruses with clinical characteristics.（NCT05523089）.

Figure 3. Schematic diagram of CDD components. (Source: CIDARA Therapeutics)

2. Polymerase inhibitors（Polymerase Inhibitors）　

Influenza virus RNA polymerase is very important for virus gene transcription and genome replication, which makes it the main goal of targeted drug design. They are highly conserved among influenza A, B, C and D viruses.^[7] Influenza virus RNA polymerase consists of three subunits: polymerase basic protein 1 in influenza A and B viruses. （PB1）Polymerase basic protein 2（PB2）And polymerase acidic protein.（PA）Or polymerase 3 protein in influenza viruses C and D.(P3) (Figure 4).

Fig. 4. Virus ribonucleoprotein (vRNP) complex model. In vRNP, the 5′ and 3′ ends of genomic antisense virus RNA (vRNA) fragment are bound by heterotrimeric RNA-dependent RNA polymerase, and the rest of vRNA is wrapped by nucleoprotein (NP). The complex is twisted into an antiparallel double helix structure, and its structure is maintained by the contact between NP monomers. The vRNA forms a loop opposite to the polymerase binding end 6. (Source: Nature)

The active sites of polymerase that bind, cleave and extend RNA are conserved in various types of influenza viruses, which is why RNA-dependent RNA polymerase is considered as the target of antiviral agents. Recently, several polymerase inhibitors have been developed for each subunit, including PB1 inhibitor favipiravir, PB2 inhibitor pimodivir and PA inhibitor baloxavir marboxil (Figure 5).

Among them, baloxavir marboxil is a relatively new drug, which belongs to hat-dependent endonuclease inhibitor.（cap-dependent endonuclease inhibitor， CENI）, a new anti-influenza drug with a new mechanism of action initiated in recent 20 years, was developed by Shionogi.（Shionogi）First developed by Pharmaceutical Co., Ltd., there is no equivalent generic drug, which has been proved to have similar symptom relief time and greater viral load reduction for healthy adults and oseltamivir.^[8]A retrospective study shows that baloxavir marboxil may reduce the hospitalization rate compared with neuraminidase inhibitors.^[9]

Fig. 5. Chemical structure of anti-influenza drugs of RNA polymerase inhibitors.

The drug resistance of Baloxavir marboxil, Favipiravir and Pimodivir and other defects highlight the need to develop other polymerase targeting molecules that can widely inhibit influenza A and B viruses.

Pre-clinical studies on various PB2-targeted small molecules are under way.^[10]At least one of them（CC-42344） In the first stage（NCT05202379）, the other one（ZSP1273）In the third stage of research(NCT04024137) (Figure 7). Substitutes for nucleoside inhibitors of Favipiravir, such as molnupiravir.(Figure 6)Because it is effective against various RNA viruses, it may be beneficial to the treatment of influenza, but they may also have teratogenic side effects similar to Favipiravir, so Merck, its developer, finally gave up the development of influenza viruses and turned to Covid-19 for treatment.The development of PB1 inhibitors based on nucleoside and non-nucleoside is in preclinical stage.^[11]But there is no clinical trial at present.

Baloxavir marboxil obviously provides a broad idea for developing polymerase inhibitor anti-influenza drugs, and many patents and in vitro studies focus on compounds or variants of Baloxavir marboxil skeleton.^[12] Although some of them have shown promising in vitro efficacy and pharmacodynamics in mice,^[13]However, candidate drugs such as AL-749 did not pass the Phase I test.

Cap-dependent endonuclease inhibitor TG-1000 (Dongyangguang Pharmaceutical)And GP681(Jiangxi Qingfeng and Yinxingshu Pharmaceutical Co-developed)Recently completed the second phase of the experiment.（NCT04706468、NCT04736758), and the recruitment of ZX-7101A phase 1 research is under way.（NCT05217732）. Various small molecules and peptides that disrupt the important protein-protein interaction between components of polymerase complex, including the key contact between PA and PB1 or between PB1 and PB2, are in the preclinical development stage.^[14]

Fig. 6. Chemical structure of a new polymerase inhibitor molnupiravir.

Fourth, the global market of anti-influenza drugs

According to the latest report released by Growth Plus Reports, the global influenza drug market is expected to reach US$ 1.51 billion by 2030, and it will grow at a compound annual growth rate of 4.8% during the forecast period. The number of influenza cases increases sharply every year, which is expected to promote the sustained growth of the influenza drug market.^[15]

North America accounts for most of the global influenza drug market.The high diagnosis rate of influenza, the wider basis of drug discovery and development, the wide availability of treatment methods, and the more significant medical expenditure contribute to the dominant position of influenza drugs in the North American market. The Asia-Pacific region has the second largest market share of influenza drugs in the world. The high prevalence rate, the government’s measures to control diseases, and the increase in health care expenditure have affected this growth.

Due to the increasing incidence of diseases and the existence of considerable influenza-related risk factors in the general population, it is expected that the European market will also see significant growth. NCBI(National Biotechnology Information Center)According to a new study, there are 27,600 respiratory deaths related to seasonal influenza in 28 EU countries every winter, of which 88% are people over 65. The mortality rate of this age group is about 35 times that of people aged 65 and under.

The main participants in the development and sales of influenza drugs include: Sanofi, Lupin, Teva, Shionogi, Macleods, Alvogen, AstraZaneca, BioCryst, La Roche, Novartis, Vitaris, etc.

V. Summary　

Although it is not as ugly as SARS-CoV-2 virus, influenza virus also kills many people, and treating influenza is still an arduous challenge for human beings. Like other antiviral drugs, the development of influenza drugs faces the difficulty of virus resistance. Baloxavir marboxil is the first new drug, which shows activity against some oseltamivir-resistant strains, and there is no significant difference in safety and effectiveness from the recently known drugs used to treat influenza. The listing of Baloxavir marboxil also brings new opportunities for combined treatment with two drugs with different mechanisms of action. Although this kind of research has not been carried out systematically, it provides a valuable new direction for influenza treatment.

In addition to Baloxavir marboxil, there are many drugs under research at different clinical stages.(Figure 7)They will be optimized in pharmacology, drug resistance, pharmacokinetics, etc., and stand on the shoulders of a few influenza drugs at present to launch a unremitting struggle against influenza virus.

Fig. 7. Overview of anti-influenza drugs in development. (Source: Antiviral Research)

References:

[1] WHO. Influenza (Seasonal). 12， 01， 2023. ↑[] Jones， J. C. et al. Influenza antivirals and their role in pandemic preparedness. Antiviral Research. 2023， 210， 105499.　

[2] Influenza (Flu) Antiviral Drugs and Related Information. FDA. 08， 12， 2022.　　

[3] Monto， A. S. et al. Influenza pandemics: history and lessons learned. Webster， R. G. et al (Eds.)， Textbook of Influenza (2 ed.)， Wiley Blackwell， West Sussex， United Kingdom (2013)， pp. 20-36　　

[4] Sugaya， N. et al. Long-acting neuraminidase inhibitor laninamivir octanoate (CS-8958) versus oseltamivir as treatment for children with influenza virus infection. Antimicrob. Agents Chemother. 2010， 54， 2575-2582

[5] Ivachtchenko， A. V. et al. Novel oral anti-influenza drug candidate AV5080. J. Antimicrob. Chemother. 2014， 69， 1892-1902.　　

[6] Peng， Q. et al. Structural insight into RNA synthesis by influenza D polymerase. Nat Microbiol. 2019， 4， 1750–1759.　　

[7] Hayden， F. G. et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescentsN. Engl. J. Med. 2018， 379， 913-923.　

[8] Komeda， T. et al. Comparison of hospitalization incidence in influenza outpatients treated with baloxavir marboxil or neuraminidase inhibitors: a health insur ance claims database studyClin. Infect. Dis.， 2021， 73， e1181-e1190.　

[9] Chen， W. et al.　 Approaches for discovery of small-molecular antivirals targeting to influenza A virus PB2 subunit. Drug Discov. Today. 2022， 27， 1545-1553.　

[10] Hou， L. et al. Contemporary medicinal chemistry strategies for the discovery and optimization of influenza inhibitors targeting vRNP constituent proteins. Acta Pharm. Sin. B. 2022， 12， 1805-1824.　　

[11] Stevaert， A. et al. The influenza virus polymerase complex: an update on its structure， functions， and significance for antiviral drug design. Med. Res. Rev. 2016， 36， 1127-1173.　

[12] Ivashchenko， A. A. et al. Synthesis， inhibitory activity and oral dosing formulation of AV5124， the structural analogue of influenza virus endonuclease inhibitor baloxavir. J. Antimicrob. Chemother. 2021， 76， 1010-1018.　

[13] Massari， S. et al. Inhibition of influenza virus polymerase by interfering with its protein-protein interactions. ACS Infect. Dis. 2021， 7， 1332-1350.

[14] Influenza Medication Market – Global Outlook & Forecast 2022-2030. Growth Plus. 11， 10， 2022.　

This article comes from WeChat WeChat official account:With freehand brushwork biotech (Biotech(ID：TXYBiotech), author: Yang Yi

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　　The biggest feature of China’s new energy automobile industry is diversification. Driven by the market and policy, the technical route of new energy vehicles presents the characteristics of multi-headed and blooming, and various explosive models such as pure electric, hybrid and hydrogen fuel cells are constantly emerging. Backed by China’s huge market demand and technical tolerance, various new energy vehicle technical routes compete on stage to compete for the mainstream. In the experience and cleansing of big waves, China’s automobile industry has also entered a period of strategic opportunities of transformation and upgrading, from big to strong.

　　Strong competitiveness attracts players to enter the hybrid car

　　Affected by rising prices of raw materials and declining subsidies, hybrid cars, once regarded as "transitional products" in the past, have shown strong market competitiveness and attracted more players to enter the competition because of their lack of mileage anxiety and good economy.

　　Hybrid models have emerged in large numbers.

　　In March, hybrid vehicles in the new energy auto market have mushroomed.

　　On March 12, BYD’s 2022 Song MAX DM-i was officially launched, and five versions were launched. After comprehensive subsidies, the price was 145,800 yuan to 172,800 yuan. As a plug-in hybrid vehicle, the Song MAX DM-i has a fuel consumption of 4.4L per 100 km, a battery life of over 1,090 km and an acceleration of only 67.9 seconds per 100 km.

　　Subsequently, BYD launched the first model of Ocean Net warship series &mdash; &mdash; Destroyer 05, the price range is 119,800 yuan to 155,800 yuan. It is understood that destroyer 05 is also equipped with DM-i super hybrid system, and still uses the combination of Xiaoyun plug-in special 1.5L high-efficiency engine, EHS electric hybrid system and super hybrid blade battery. The comprehensive cruising range is more than 1200km when full of oil and electricity. It is worth mentioning that the 120km version of destroyer 05 has also added functions such as VTOL mobile power station and 17kW DC fast charging port, which unlocked more car scenes.

　　Then, BYD’s most important super-mixed flagship model, Han DM series, officially opened for pre-sale on March 19. Among them, Han DM-i, which focuses on the ultimate energy saving, has a pure battery life of 242km under NEDC working conditions, a fuel consumption of 4.2L per 100 km, and a comprehensive battery life of 1300km；; Han DM-p, which focuses on excellent performance, takes only 3.7 seconds to accelerate in one hundred kilometers. Under NEDC working conditions, the pure battery life is 202km, and the fuel consumption per 100 kilometers is only 5.2L.

　　Driven by BYD, Great Wall, Geely and Chery have also joined the development of hybrid vehicles.

　　On March 1st, the hybrid model Wei Mocha DHT-PHEV under Great Wall Motor was officially launched, and two models were launched, with the price range of 295,000 yuan to 315,000 yuan. In terms of power, Moka DHT-PHEV is equipped with a DHT plug-in hybrid system consisting of "1.5T gasoline direct injection engine +130KW front drive motor +135KW rear drive motor", which can achieve an ultra-long pure electric cruising range of more than 200km and a comprehensive cruising range of more than 1000km, and the fuel consumption per 100km is only 5.55L, showing the good strength of lemon hybrid DHT platform.

　　Chery’s hybrid model Star Road Chasing Wind ET-i was also pre-sold on March 2nd. This car is equipped with Chery’s newly-developed Star Core ET-i full-engine super hybrid technology, which is composed of a 1.5T four-cylinder turbocharged engine and dual motors. The maximum torque can reach 230N·m, the official acceleration is 6.8 seconds, and the comprehensive battery life is as high as 1000km.

　　Geely Group also officially listed the hybrid version of Xingyue L Raytheon Hi·X on March 30, and the official guide price was 171,700 yuan to 183,700 yuan. The biggest highlight of the car is that it is equipped with the Geely Lei Shenqing Hi·X hybrid system for the first time, with a comprehensive fuel consumption of 4.3L per 100 kilometers and a maximum cruising range of 1300km.

　　Obviously, the hybrid version of Xingyue L Raytheon Hi·X has reached a better balance point in terms of power performance and fuel economy. Its arrival will not only further enrich the car series of Xingyue L, but also help Geely Automobile seize the hybrid market.

　　Technology platforms have their own advantages.

　　Behind the emergence of a large number of hybrid vehicles, the technological breakthrough of independent brands in the field of new energy vehicles has emerged.

　　In the past, the hybrid field has always been dominated by Toyota and Honda in Japan, and other brands are more like "bystanders". Nowadays, with the growing strength of China’s head car enterprises, more and more independent brands begin to show their technological achievements in the hybrid field.

　　At the beginning of 2021, BYD officially released the DM-i super hybrid system. As the first domestic hybrid system, it is different from the "oil hybrid" route centered on the engine in structure. BYD DM-i super hybrid system has chosen the "electric hybrid" route with electric drive as the main part, which has made an essential breakthrough in technology.

　　Different from most people’s traditional hybrid mode, BYD DM-i super hybrid system is based on super-safe large-capacity battery and high-performance high-power flat-wire motor, which changes the traditional hybrid technology mainly relying on engine and oil, thus greatly reducing fuel consumption. In daily use, when the power is sufficient, this DM-i super hybrid system is mainly driven by high-power and high-efficiency motors, and the main function of the gasoline engine is to generate electricity in the high-efficiency rotating speed region, so as to realize the characteristics of using more electricity, using less oil and using oil efficiently; When the power is insufficient, the DM-i super hybrid becomes a hybrid system with ultra-low fuel consumption.

　　At present, BYD’s DM-i super hybrid system has achieved full coverage from cars to SUVs, and almost all of them are "explosive models", which has become a "textbook-level" sales model in the new energy market.

　　The lemon hybrid DHT technology introduced by Great Wall Motor at the end of 2020 fully takes into account China’s national conditions, which not only continues the excellent performance of Japanese brands at low speed, but also strengthens the power output at high speed.

　　From the structural principle, compared with the single-speed hybrid of Honda i-MMD (when driving at high speed, the engine can only directly drive the vehicle through a fixed gear), the Great Wall lemon hybrid DHT system pioneered the introduction of multi-gear direct drive technology, which can realize two-speed hybrid at high speed. When power is needed, the engine can amplify torque by downshifting to ensure power output, while when cruising is resumed, upshifting will reduce the speed and ensure good economy.

　　Compared with lemon hybrid DHT, the official explanation of Chery Kunpeng DHT is more straightforward, which is called "Dedicated Hybrid Transmission", which is also a special gearbox for hybrid power.

　　According to the information disclosed at present, the hybrid platform has the first dual-motor driven DHT gearbox in China. Combined with Chery’s FIO fixed-point injection oil-cooled motor technology, TEM ultra-efficient dual-motor power distribution technology, ultra-smooth TSD dual-shaft drive design and other hybrid integrated technologies, even in the low-power mode, the fuel saving rate is still more than 50%, and the energy saving effect is quite eye-catching.

　　Different from other brands, Geely has gone in another direction on the road of mixing. In order to pursue the ultimate fuel consumption performance, the Hi·X system of Geely Ray Shenqing did not directly choose the series-parallel hybrid technology, but used the planetary gear system for high-efficiency power splitting.

　　First of all, Geely specially developed the DHE15(1.5TD) engine for this hybrid system, and its thermal efficiency reached 43.32%. Secondly, Lei Shenqing Hi·X also owns the world’s first mass-produced 3-speed hybrid transmission &mdash; &mdash; DHT Pro makes the engine have more chances to be in an efficient working area; In addition, Lei Shenqing Hi X also has a big point of view, that is, its full-speed parallel connection. According to the manufacturer, the model equipped with Lei Shenqing Hi X power can enter the parallel mode when the speed is above 20km/h, realizing the ejection start, which is much lower than the parallel speed of Japanese hybrid cars at least 70km, and the system efficiency is improved by 20%.

　　Show strong market competitiveness

　　With the blowout of the new energy vehicle market, the hybrid vehicle once considered as a "transitional product" has become one of the main forces in the new energy vehicle market because of the lack of mileage anxiety, good driving experience and policy dividends in some regions.

　　According to the data released by China Association of Automobile Manufacturers, in 2021, the sales volume of new energy passenger cars in China reached 3.334 million, up 120.6% year-on-year. Among them, the sales volume of plug-in hybrid vehicles (PHEV) reached 600,000, with a growth rate of 121.6%, even slightly exceeding the growth rate of pure electric vehicles.

　　After entering 2022, the plug-in hybrid vehicle market is experiencing explosive growth. According to the data of China Association of Automobile Manufacturers, from January to February this year, 160,000 plug-in hybrid vehicles were sold, a year-on-year increase of 2.5 times. Among them, the sales volume of plug-in hybrid vehicles in February was 75,000, a year-on-year increase of 3.4 times.

　　In the industry’s view, under the background that pure electric vehicles can’t completely solve the mileage anxiety and face the problems of rising battery cost and tight supply, the "transitional product" of hybrid vehicles has attracted more players to enter the competition and presented a scene of "letting a hundred flowers blossom".

　　It is understood that in addition to BYD, Great Wall Motor and Geely, Changan Automobile also launched its own blue whale iDD hybrid system, and on March 10, it listed the plug-in hybrid model Changan UNI-K iDD；; Nezha Auto also announced that it will mass-produce the first extended-range model; The new car jointly launched by Xiaokang and Huawei not long ago &mdash; &mdash; AITO Wenjie M5 is also an extended-range medium-sized SUV.

　　According to industry analysts, although the sales of pure electric vehicles are increasing day by day, due to imperfect supporting facilities and imperfect power battery material system, pure electric vehicles cannot completely replace traditional fuel vehicles in a short time, which gives opportunities for the development of hybrid vehicles. At the same time, car companies have recently launched many explosive hybrid models. While opening up the hybrid car market, they have also undertaken the heavy responsibility of fuel vehicle transformation.

　　In this regard, Cui Dongshu, secretary-general of the Association, said recently that "in 2022, there will be more than 500,000 A-class plug-in hybrid vehicles, and plug-in hybrid products of independent brands are worth looking forward to." In his view, plug-in hybrid vehicles will usher in explosive growth in the A-class new energy market: on the one hand, due to rising raw material prices and the impact of subsidies, pure electric vehicles have begun to increase prices, but plug-in hybrid vehicles have been less affected; On the other hand, the rise in oil prices has also caused many consumers to turn to plug-in hybrid vehicles with lower fuel consumption.

　　Xu Haidong, deputy chief engineer of China Automobile Association, predicted that "in the next decade, the hybrid market will have a lot of room for growth to make up for the shortcomings of pure electric vehicles in terms of mileage anxiety, insufficient charging convenience and declining battery life in winter." (Fu Yong)

　　Market demand for electric technology for heating and extending range

　　China’s new energy automobile industry has entered the stage of "two-wheel drive" in market and policy, and many technical lines show the characteristics of multi-head progress and blooming flowers. According to the insiders, the long-term parallel operation of extended-range electric, hybrid and pure electric is the best route combination to accelerate the large-scale replacement of fuel vehicles by new energy sources and realize China brand surpassing overseas brands. Among them, the extended-range electric provides the solution of "urban electricity consumption and long-distance power generation", which meets the diversified car demand of users and is increasingly valued and recognized by the market.

　　Many car companies have laid out extended-range electric vehicles.

　　According to public data, in 2021, the sales volume of new energy vehicles in China was 3.521 million, a year-on-year increase of 160%, ranking first in the world for seven consecutive years. It is particularly worth mentioning that compared with the initial period of the Thirteenth Five-Year Plan, the proportion of private consumption of new energy vehicles has increased from 47% to 78%, and the proportion of private consumption in non-restricted cities has increased from 40% to 70%.

　　Driven by market and policy, the technical lines of new energy vehicles show the characteristics of multi-head and multi-flowers. Technical lines such as charging and replacing pure electric vehicles, extended-range electric vehicles, hybrid electric vehicles, fuel cell electric vehicles, hydrogen fuel vehicles and methanol vehicles have blossomed in an all-round way, achieving good social and economic benefits, and a number of head brands with excellent technology and market recognition have emerged.

　　Regarding the energy utilization line of passenger cars, Li Xiang, chairman of LI, said at the 2022 China Electric Vehicle committee of 100 Forum on March 26: "Today, so many people are willing to buy new energy vehicles because new energy vehicles meet their needs." In Li Xiang’s view, the demand of new energy owners is mainly concentrated in three aspects: first, the convenience of energy acquisition; The second is the cost of energy acquisition; The third is environmental protection.

　　Li Xiang calculated an account: "The cost of charging an extended-range electric vehicle at home can be as low as less than a dime per kilometer; The cost of using public charging facilities is about 2 to 4 cents per kilometer; In contrast, the use cost of fuel vehicles reaches 6 to 8 cents per kilometer. If it is combined with the convenience of charging, the advantages of electric vehicles are more obvious. "

　　In fact, as an important force in the technical circuit of new energy vehicles, extended-range electric vehicles not only retain the excellent driving performance, low use cost and low-carbon environmental protection characteristics of electric vehicles, but also realize the advantages of endurance and recharge comparable to fuel vehicles, which is getting more and more attention and recognition from the market.

　　At present, in addition to LI, Dongfeng, Huawei and other enterprises have laid out the field of extended-range intelligent electric vehicles, such as Li ONE, Lantu FREE, AITO Wenjie M5 and Mocha DHT-PHEV.

　　Give the option to the market

　　From a policy perspective, supporting the diversification of new energy technology routes has always been the meaning of various industry guidance documents. For example, the "Technology Roadmap 2.0 for Energy-saving and New Energy Vehicles" released not long ago particularly emphasized that the choice of technology route should be given to the market.

　　The industry generally believes that technologies such as extended range, pure electricity and plug-in hybrid will coexist for a long time in the future.

　　Xu Lin, chief technology officer of Xiaokang Group and president of Celeste (rotating), said: "Pure electric vehicles are more suitable for users who commute mainly in cities, while for users who often have to run long distances, electric vehicles with oil and electricity will be more suitable. We should leave the choice to consumers."

　　Liu Hanru, the chief scientist of Geely Commercial Vehicle Group, also said that the new generation of commercial vehicles with green and intelligent technologies as the core will gradually replace traditional fuel vehicle products. As one of the core three-electric systems of electric-driven commercial vehicles, the cost of power battery directly affects the selling price of market terminals. Therefore, commercial vehicle enterprises should also consider more possibilities besides pure electric drive and attach importance to the diversified development of energy technology routes in the process of new energy transformation.

　　In this respect, LI has determined several key points since its establishment: firstly, it firmly adopts the technical scheme of pure electric drive and extended-range electric drive; secondly, considering solving users’ mileage anxiety and the convenience of replenishing energy, and effectively reducing carbon emissions, LI has provided a solution of "using electricity in cities and generating electricity for a long distance" to reflect the important characteristics and advantages of extended-range electric technical lines.

　　"In the past, the traditional PHEV had a big problem. Its pure battery life was generally only over 50 kilometers, which could not meet the needs of urban use. And when the power is exhausted, the energy consumption of the vehicle will become higher. " Li Xiang explained that through the investigation of urban users, it was found that if the cruising range of pure electricity can exceed 150 kilometers, it can cover all major cities in the world. "So, LI has set its goal to be an extended-range electric vehicle of more than 150 kilometers."

　　Based on the success of Li ONE, more and more China automobile brands began to follow the extended-range electric technology, and have determined higher pure electric cruising range. At present, the pure electric cruising range of a large number of PHEV models has reached 150 kilometers or even more than 200 kilometers.

　　Extended range electric technology is beneficial to carbon reduction.

　　For the extended-range electric technology, some people have also raised questions: Is the extended-range electric vehicle to cater to the "compromise line" of users without charging conditions? How significant is it for reducing carbon emissions?

　　In this regard, Li Xiang said that 70% of users in LI have installed home charging piles, and more than 90% have fixed charging conditions. The actual results of operation in the past two years show that in major cities such as Beishangguangshen and Shenzhen, the average mileage of LI car owners is 70%, and the total driving time is over 80%.

　　The data is the best proof. According to Li Xiang, in terms of energy conservation and emission reduction, Li ONE’s carbon emissions can be reduced by 65% compared with the same level of fuel vehicles; If you focus on cities like Beijing, carbon emissions can be reduced by 76%.

　　It is reported that during this year’s Beijing Auto Show, LI will release its new product Ideal L9. "Through technical optimization, our battery life has reached more than 200 kilometers and the thermal efficiency has increased by 15%." Li Xiang said: "In the future, through a new generation of people’s extended-range technology and a new intelligent operation mode, we are very confident that we can reduce the carbon emission target in cities from the current 76% to more than 90%."

　　Li Xiang believes that at present, China’s automobile industry has entered a strategic opportunity period of transformation and upgrading, from large to strong. Driven by strong domestic demand, central electric energy and distributed liquid energy will coexist for a long time in the future, and jointly promote the realization of the "double carbon" goal. (Li Tangning)