Arbidol: the Drug with Possible Use for Treating SARS-CoV-2

 In Blog Post, SARS-CoV-2


In the past few months, this drug has gained particular relevance in the light of the outbreak of pneumonia that began in December 2019 in the Chinese city of Wuhan. The contagious agent is the previously unknown SARS-CoV-2. Cases of infection and death have been increasing over the past few months. The virus is transmitted from person to person. The risk of infection is very high. Cases of infection are recorded in Thailand, Australia, Singapore, Japan, the USA, Germany, France, etc. (188 countries in total) So far, the effectiveness of any drugs against coronavirus SARS-CoV-2 has not been reported. 

Today, the problem of treating influenza and other viral diseases is extremely urgent because they make up an impressive share of all infectious diseases. Every year in the winter months, influenza spreads over several continents

 According to the World Health Organization (WHO), 5–10% of adults and 20–30% of children suffer from influenza every year, while terminal episodes amount to around 250–500 thousand people. Fortunately, the human body is equipped with the immune system, a means of protection against foreign microorganisms. The difficulty lies in the fact that it usually takes the system around several days (although this varies person to person) to develop “weapons”, interferons and antibodies, in quantities sufficient to struggle with the disease. Symptoms can last 3-8 days, with the possibility of the cough lasting up to two months.

SARS-CoV-2
Representation of the SARS-CoV-2 Virus – Although it does not necessarily express HE, it does express spike protein and Arbidol interacts with this, and several membrane proteins.

In the context of the spreading virus, it is important to remember about prevention as much as about the treatment itself. Doctors recommend the following preventive measures to reduce the risk of infection:  

  1. If possible, avoid crowded places, wear protective masks in vehicles and stores. 
  2. Coronavirus is spread not only by airborne channels but also by the non-percutaneous ones, therefore, it is necessary to stick to strict hygiene rules, including frequent handwashing with soap, rinsing the nasopharynx with salt water and using disinfectants wherever possible. 
  3. Some experts also recommend helping immunity through natural means: eating products that are rich in vitamins and taking immunostimulants.

The pharmaceutical and scientific industries have developed tools to help the immune system accelerate recovery, reduce the effects of infection, and to prevent morbidity. The development of a broad-spectrum antiviral drug capable of suppressing influenza and other acute respiratory viral infections (ARVI) in the middle of the last century. In 1974 scientists of the All-Union Scientific Research Chemical-Pharmaceutical Institute, Institute of Medical Radiology of the USSR Academy of Medical Sciences and the Leningrad Bacteriological and Diagnostic Institute developed an antiviral drug Arbidol®.

Arbidol® is one of the most widely used antiviral medications worldwide and is included on a G20 nations list of vital drugs1https://en.wikipedia.org/wiki/G20.. Arbidol® is a broad-spectrum antiviral compound used in the treatment of influenza caused by A and B infections (including swine and avian) and other ARVI and rotavirus pathogens. The drug had been developed for more than a decade. During this period, in the course of many medical trials, the information had been obtained about its high safety and efficacy. This makes it possible to prescribe the medicine not only for adults but also for children. 

The active ingredient of the drug is Umifenovir. This substance exhibits antiviral and immunomodulating properties. Basically this is what happens in the case of Influenza:

  • The virus has a special haemagglutinin protein on its surface, with which it attaches to the outer membrane of a host cell. 
  • After attaching to the cell membrane, the virus is enveloped by the cell membrane and enters the cell in the form of an endosome vesicle (a sort of intracellular transport vehicle) for further reproduction.
  • Arbidol® (Umifenovir), blocks the haemagglutinin protein, does not allow the virus to penetrate into the cell, sealing it (the virus) inside the endosome, where it dies. 
In this example, one can imagine the haemagglutinin which is usually not expressed in SARS-CoV-2 replaced by another docking protein, such as Nsp7_Nsp8 complex, Nsp14, Nsp15, E-channel, or Spike protein.

Thus, Arbidol® acts as an inhibitor of the fusion between the virus and the cells of the mucosal membranes of the upper respiratory tract. Accordingly, the most effective period for taking the drug is in the first hours of the disease, when the virus has not yet had time to invade the cell. The possibility of using the drug Arbidol® in ARVI of various types is due to its universal mechanism of action as described above (viral fusion). Due to this mechanism of action, Arbidol® has a wide spectrum of antiviral activity against viruses that cause various acute respiratory infections, including viruses from the Coronaviridae family, as stated on the main page of the official website of the drug 2https://arbidol.ru/

Studies have shown that Arbidol, compared with untreated control groups effectively inhibits coronavirus up to 60x at concentrations of 10–30 μmol/L, and ‘significantly inhibit the virus’ pathological effect on cells’3https://www.sciencedirect.com/science/article/pii/S2211383520302999

Pubmed.gov, which is one of the most authoritative sources of medical publications in the world, has a significant number of double-blind, randomized, placebo-controlled tests of Umifenovir, showing its effectiveness against influenza and ARVI 4https://www.ncbi.nlm.nih.gov/pubmed/31094461

Note: the main adverse effects when taking the drug are nausea, diarrhoea, dizziness and elevated serum transaminase (5https://www.cochranelibrary.com/es/cdsr/doi/10.1002/14651858.CD011489/full/es) and the rate of occurrence is around 6.2% – given that there is roughly a two week incubation period we recommend only using this as a prophylactic if you have a high risk of exposure.

The existence and use of Arbidol® in medical practice has been recognised internationally. At the end of 2013, the active substance of the drug Arbidol® (Umifenovir) was included in the group of direct-acting antivirals (J05A) of the Anatomical-therapeutic-chemical classification (ATC) – the international drug classifier. 

Despite the fact that Arbidol® is not an FDA certified drug, it is considered one of the most popular antiviral agents in Russia, and it is also actively used in some CommonWealth of Independent States countries. In Kazakhstan, it is produced under the brand name Afludol, in Belarus, the drug is known as Arpetol and Arpeflu, and the Kiev pharmaceutical company ‘Darnitsa’ produces it under the brand name Immustat. Umifenovir is also available in the Netherlands under the name Orvitol NP. Umifenovir is actively used in China as well. 

However, the National Health Commission of the People’s Republic of China published the sixth version of the preliminary plan for the diagnosis and treatment of the disease, which included the drug with the active substance Umifenovir (Arbidol®). The drug was included in a large-scale program for testing possible medications that can alleviate the course of the disease. Chinese experts recommend taking 200 mg (2 capsules) for adults, daily 3 times / day6http://www.nhc.gov.cn/yzygj/s7652m/202002/54e1ad5c2aac45c19eb541799bf637e9.shtml). It is not recommended that you use 3 or more antiviral drugs at the same time. The drug administration should be discontinued if any side effects occur. 

According to Li Lanjuan a virologist and an adviser to the National Health Commission of China, Umifenovir demonstrates the capability to inhibit the pathological effect of coronavirus, SARS-CoV-2 on cells in vitro. The Chinese manufacturer SSY Group Limited assures that the drug can stimulate the production of interferons by the body of the patient suffering from coronavirus. 

However, the effectiveness of Arbidol® in the treatment of coronavirus is yet to be proven. This will take some time because the term “proven effectiveness” means that the medication has been used to treat a wide range of patients in many different medical institutions, and over a long period of time the consequences of such use have been observed. In addition to Arbidol®, the program includes about 30 other drugs, among them Chloroquine Phosphate, and a combination of Ribavirin and Interferons, as well as some methods from Chinese alternative medicine.

It is obvious that in the fight against the novel virus we need to act fast. In these terms, many experts point out that Umifenovir indeed may be able to reduce the severity of the disease. According to the WHO Guidelines for Solving the Ethical Problems in Infectious Diseases, if during an epidemic there are no drugs with proven effectiveness, it is permissible to include potentially effective drugs in national recommendations. In this regard, in order to save the lives of patients who are diagnosed with coronavirus, doctors may prescribe all drugs that have at least a potential chance to affect the virus – including Umifenovir (Arbidol®). Here is one of the latest Chinese studies on Arbidol® in terms of coronavirus: 7https://www.ncbi.nlm.nih.gov/pubmed/32037389.

If you feel unwell, immediately consult the doctor. The sooner the patient begins the treatment, the more likely it is for them to recover and the more likely it is that they will not infect others- family members and loved ones are the most at risk.

Footnotes

  1. Wikipedia Contributors (2020). G20. [online] Wikipedia. Available at: https://en.wikipedia.org/wiki/G20 [Accessed 8 Mar. 2020].
  2. Arbidol.ru. (2013). Препарат Арбидол — лекарство от простуды и гриппа для взрослых и детей с 3-х лет. [online] Available at: https://arbidol.ru/ [Accessed 8 Mar. 2020].
  3. Wu, C., Liu, Y., Yang, Y., Zhang, P., Zhong, W., Wang, Y., Wang, Q., Xu, Y., Li, M., Li, X., Zheng, M., Chen, L. and Li, H. (2020). Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B. [online] Available at: https://www.sciencedirect.com/science/article/pii/S2211383520302999 [Accessed 10 Mar. 2020].
  4. ‌Pshenichnaya, N.Y., Bulgakova, V.A., Lvov, N.I., Poromov, A.A., Selkova, E.P., Grekova, A.I., Shestakova, I.V., Maleev, V.V. and Leneva, I.A. (2019). Clinical efficacy of umifenovir in influenza and ARVI (study ARBITR). Terapevticheskii arkhiv, [online] 91(3), pp.56–63. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31094461 [Accessed 8 Mar. 2020].
  5. Huang, L., Zhang, L., Liu, Y., Luo, R., Zeng, L., Telegina, I. and Vlassov, V.V. (2015). Arbidol for preventing and treating influenza in adults and children. Cochrane Database of Systematic Reviews. [online] Available at: https://www.cochranelibrary.com/es/cdsr/doi/10.1002/14651858.CD011489/full/es [Accessed 8 Mar. 2020].
  6. Nhc.gov.cn. (2020). 《新型冠状病毒肺炎诊疗方案(试行第六版)》解读. [online] Available at: http://www.nhc.gov.cn/yzygj/s7652m/202002/54e1ad5c2aac45c19eb541799bf637e9.shtml [Accessed 8 Mar. 2020].
  7. Wang, Z., Chen, X., Lu, Y., Chen, F. and Zhang, W. (2020). Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Bioscience trends, [online] p.10.5582/bst.2020.01030. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32037389 [Accessed 8 Mar. 2020].

Translated footnote 6 link: https://translate.google.com/translate?hl=en&sl=zh-CN&u=http://www.nhc.gov.cn/yzygj/s7652m/202002/54e1ad5c2aac45c19eb541799bf637e9.shtml&prev=search

‌If you’re interested in antivirals and immunostimulants check out our recent blog post on other medicines that are useful against airborne respiratory viral illnesses.

Link to a reputable Arbidol (Umifevonir) seller here

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