key: cord-1030273-wpo99v5h
authors: Dabrowska, Agnieszka; Szczepanski, Artur; Botwina, Paweł; Mazur-Panasiuk, Natalia; Jiřincová, Helena; Rabalski, Lukasz; Zajic, Tomas; Popowicz, Grzegorz; Pyrc, Krzysztof
title: Efficacy of antiviral drugs against the omicron variant of SARS-CoV-2
date: 2021-12-23
journal: bioRxiv
DOI: 10.1101/2021.12.21.473268
sha: f76783360aa55308d0aa4d4bbf8aec8ff67df6c1
doc_id: 1030273
cord_uid: wpo99v5h

The Omicron variant of the SARS-CoV-2 virus was first detected in South Africa in November 2021. The analysis of the sequence data in the context of earlier variants suggested that it may show very different characteristics, including immune evasion and increased transmission. These assumptions were partially confirmed, and the reduction in protection in convalescent patients and vaccinated individuals have been confirmed. Here, we have evaluated the efficacy of antivirals against SARS-CoV-2 variants, Omicron, Delta, and the early 2020 isolate.

The SARS-CoV-2 virus emerged in 2019 in South-Eastern Asia, to spread rapidly in 2020 to all continents and cause the global pandemic. In 2020, several variants of the virus emerged, but none became dominant for a long time; however, the end of 2020 brought us the alpha variant that emerged in the United Kingdom, to cause the winter wave of infections in many countries. However, its prime position was abolished during the spring/summer season by the delta variant, first detected in India in the late 2020. These viruses were characterized mainly by the increased transmissibility, as the need for more effective transmission mainly drove their evolution. In the meantime, several variants evading the immune responses were identified. The beta variant was first detected in autumn 2020, Lambda was in August 2020, and Mu in January 2021. All these variants carried mutations localized to the epitopes recognized by the neutralizing antibodies. However, due to evolutionary inferiority, they have never become As it is known that the efficacy of vaccines and some monoclonal antibodies is reduced, it is of importance to verify whether the small molecule drugs targeting the more conserved proteins remain effective. We focused mainly on the drugs that went successfully through the To test the antiviral activity of the compounds, subconfluent A549 ACE2+TMPRSS2+ cells 10 were infected with viruses (all three variants) at 1600 50% tissue culture infectious dose (TCID50)/ml in the presence of selected concentrations of inhibitors. Control was prepared in the same manner, but no inhibitor was added. After 2 h of incubation at 37°C, cells were rinsed twice with PBS, and a fresh medium with compounds was added. The infection was carried out for 72 h, and the cytopathic effect (CPE) was assessed. Culture supernatants were collected for analysis, which was carried out as previously described 7 . The experiment was performed in three biological repetitions, each in duplicate (n=6). The half maximal inhibitory concentration (IC50) value was calculated using GraphPad Prism 9.0. Obtained results are presented in Figure   1A -F and the estimated IC50 values are presented in Figure 1G . For paxlovid, molnupiravir, acriflavine and remdesivir the observed inhibition and IC50 was similar as described previously, and maintained for all the variants. We did not, however, observe the activity of AT-527, but this is most likely associated with the model itself and the inability of cells to process the inert pro-drug to its active metabolite. Concluding, the obtained results show that the drugs that are being developed against the SARS-CoV-2 will likely retain its efficacy also for the omicron variant.

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