NUCLEOSIDE ANALOG FAVIPIRAVIR IS A POOR INHIBITOR AGAINST THE SARS-COV-2 VIRUS IN CELL CULTURE, BUT FAVIPIRAVIR IS HIGHLY ACTIVE AGAINST VENEZUELAN EQUINE ENCEPHALITIS VIRUS

Abstract

The SARS-CoV-2 pandemic has been the largest epidemiological event in the current century, however, it was not the first epidemic with a large tally in the 21st century, nor it will be the last. The majority of pathogens which have caused large epidemics in the 21st century (avian influenza, pandemic influenza, MERS, Ebola, etc.), including the SARS-CoV-2 itself, are RNA-containing viruses. The biological nature of the pathogen which will cause the future epidemic is difficult to predict, but with it highly probable will be an RNA-containing virus. To prepare for future epidemics, drug repurposing is a promising approach. The drugs repurposing against RNA viruses is facilitated by pathogens’ features such that RNA-dependent RNA polymerases have the ability to incorporate modified nucleotides into growing RNA strands; and in the majority RNA viruses, their replicases do not have the editing capacity.

In this work, we measured the ability of two registered antiviral drugs with different mechanisms of antiviral action - Favipiravir and Cycloferon - to suppress the replication of two unrelated viruses in Vero E6 cell culture. We measured the antiviral activity against the coronavirus SARS-CoV-2 and Venezuelan equine encephalitis virus (VEEV).

Favipiravir was not an effective inhibitor of SARS-CoV-2, because of the high half-maximal effective concentration, EC50 > 6.67 mg/ml. But Favipiravir actively suppressed the replication of the VEEV virus in the pharmacological concentration range.

Cycloferon appeared to be a prominent inhibitor of the SARS-CoV-2 cotonavirus, demonstrating EC50 = 0.066 mg/ml. However, Cycloferon was ineffective against VEEV.

Such differences in the activity of two drugs against two unrelated RNA-viruses are probably explained by different mechanisms of the antiviral action.