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Chemically, umifenovir features an
indole core, functionalized at all but one positions with different substituents. The molecular groups of umifenovir - hydroxy, amino and carboxy - can interact to form various hydrogen-bonded synthons. Antiviral activity and acceptable cytotoxicity profiles [7][8] make it a promising candidate for further research as a potential therapeutic agent for the selective treatment of flavivirus infections [9]. Umifenovir is characterized by only one polymorphic form but can exist in the form of a large number of crystal solvates, the production of which depends on the medium and conditions of synthesis. In this case, the implementation of the crystal solvate or other solid form may be determined by the spatial structure and conformational equilibria in the saturated solution [10][11]. The drug has been shown in studies to inhibit viral entry into target cells [12] and stimulate the immune response.
Status
Testing of umifenovir's efficacy has mainly occurred in China and Russia,[13][14] and it is well known in these two countries.[15] Some of the Russian tests showed the drug to be effective[13] and a direct comparison with
oseltamivir showed similar efficiency in vitro and in a clinical setting.[16] In 2010 Arbidol was the drug brand with the highest sales volume in Russia.[17] In the first quarter of 2020 it had a 16 percent share in the Russian antiviral market.[18]
Mode of action
Biochemistry
Umifenovir inhibits membrane fusion of influenza virus.[5] Umifenovir prevents contact between the virus and target host cells. Fusion between the viral envelope (surrounding the
viral capsid) and the
cell membrane of the target cell is inhibited. This prevents viral entry to the target cell, and therefore protects it from infection.[19]
Some evidence suggests that the drug's actions are more effective at preventing infections from
RNA viruses than infections from
DNA viruses.[20]
More recent studies indicate that umifenovir also has in vitro effectiveness at preventing entry of
Zaire ebolavirus (Kikwit strain), Tacaribe
arenavirus and
Kaposi's sarcoma-associated herpesvirus in mammalian cell cultures, while confirming umifenovir's suppressive effect in vitro on
Hepatitis B and
poliovirus infection of mammalian cells when introduced either in advance of viral infection or during infection.[23][24]
In 2007, the Russian Academy of Medical Sciences stated that the effects of Arbidol (umifenovir) are not scientifically proven.[26]
Russian media criticized lobbying attempts by
Tatyana Golikova (then-Minister of Healthcare) to promote umifenovir,[27] and the unsubstantiated claim that Arbidol can speed up recovery from flu or cold by 1.3-2.3 days.[28] They also made claims that comparative clinical studies have proven umifenovir to be inefficient.[29][30]
In early 2020 umifenovir was touted as a potential treatment for
COVID-19 in China, where it was sometimes given to patients in combination with other drugs such as the anti-HIV drug
Darunavir.[32][33][34][35] A three-arm RCT study published in May 2020 in the
Cell Press journal Clinical Advances found that neither Umifenovir or
Lopinavir/
Ritonavir helped patients with mild to moderate COVID-19.[36] A similar study comparing Umifenovir directly with Lopinavir/Ritonavir found no difference in fever duration between the two groups but found a lower viral load on day 14 in the Umifenovir group.[37] A systemic review and meta-analysis of 16 studies on Umifenovir published in March 2021 concluded that there is "no significant benefit of using Arbidol compared with non‐antiviral treatment or other therapeutic agents against COVID‐19 disease."[38]
^
abLeneva IA, Russell RJ, Boriskin YS, Hay AJ (February 2009). "Characteristics of arbidol-resistant mutants of influenza virus: implications for the mechanism of anti-influenza action of arbidol". Antiviral Research. 81 (2): 132–140.
doi:
10.1016/j.antiviral.2008.10.009.
PMID19028526.
^Wang MZ, Cai BQ, Li LY, Lin JT, Su N, Yu HX, et al. (June 2004). "[Efficacy and safety of arbidol in treatment of naturally acquired influenza]". Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae. 26 (3): 289–293.
PMID15266832.
^Boriskin YS, Leneva IA, Pécheur EI, Polyak SJ (2008). "Arbidol: a broad-spectrum antiviral compound that blocks viral fusion". Current Medicinal Chemistry. 15 (10): 997–1005.
doi:
10.2174/092986708784049658.
PMID18393857.
^Shi L, Xiong H, He J, Deng H, Li Q, Zhong Q, et al. (2007). "Antiviral activity of arbidol against influenza A virus, respiratory syncytial virus, rhinovirus, coxsackie virus and adenovirus in vitro and in vivo". Archives of Virology. 152 (8): 1447–1455.
doi:
10.1007/s00705-007-0974-5.
PMID17497238.
S2CID13595688.
^Glushkov RG, Gus'kova TA, Krylova LI, Nikolaeva IS (1999). "[Mechanisms of arbidole's immunomodulating action]". Vestnik Rossiiskoi Akademii Meditsinskikh Nauk (in Russian) (3): 36–40.
PMID10222830.