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Snake venom phospholipases A2 possess a strong virucidal activity against SARS-CoV-2 in vitro and block the cell fusion mediated by spike glycoprotein interaction with the ACE2 receptor

Andrei E. Siniavin, Maria A. Nikiforova, Svetlana D. Grinkina, Vladimir A. Gushchin, Vladislav G. Starkov, Alexey V. Osipov, Victor I. Tsetlin, Yuri N. Utkin
doi: https://doi.org/10.1101/2021.01.12.426042
Andrei E. Siniavin
1Department of Molecular Neuroimmune Signalling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia
2N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia
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  • For correspondence: andreysi93@ya.ru yutkin@yandex.ru utkin@ibch.ru
Maria A. Nikiforova
2N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia
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Svetlana D. Grinkina
2N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia
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Vladimir A. Gushchin
2N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia
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Vladislav G. Starkov
1Department of Molecular Neuroimmune Signalling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia
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Alexey V. Osipov
1Department of Molecular Neuroimmune Signalling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia
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Victor I. Tsetlin
1Department of Molecular Neuroimmune Signalling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia
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Yuri N. Utkin
1Department of Molecular Neuroimmune Signalling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia
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  • For correspondence: andreysi93@ya.ru yutkin@yandex.ru utkin@ibch.ru
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Abstract

A new coronavirus was recently discovered and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the absence of specific therapeutic and prophylactic agents, the virus has infected almost hundred million people, of whom nearly two million have died from the viral disease COVID-19. The ongoing COVID-19 pandemic is a global threat requiring new therapeutic strategies. Among them, antiviral studies based on natural molecules are a promising approach. The superfamily of phospholipases A2 (PLA2s) consists of a large number of members that catalyze the hydrolysis of phospholipids at a specific position. Here we show that secreted PLA2s from the venom of various snakes protect to varying degrees the Vero E6 cells widely used for the replication of viruses with evident cytopathic action, from SARS-CoV-2 infection PLA2s showed low cytotoxicity to Vero E6 cells and the high antiviral activity against SARS-CoV-2 with IC50 values ranged from 0.06 to 7.71 μg/ml. Dimeric PLA2 HDP-2 from the viper Vipera nikolskii, as well as its catalytic and inhibitory subunits, had potent virucidal (neutralizing) activity against SARS-CoV-2. Inactivation of the enzymatic activity of the catalytic subunit of dimeric PLA2 led to a significant decrease in antiviral activity. In addition, dimeric PLA2 inhibited cell-cell fusion mediated by SARS-CoV-2 spike glycoprotein. These results suggest that snake PLA2s, in particular dimeric ones, are promising candidates for the development of antiviral drugs that target lipid bilayers of the viral envelope and may be good tools to study the interaction of viruses with host cell membranes.

Competing Interest Statement

The authors have declared no competing interest.

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Posted January 12, 2021.
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Snake venom phospholipases A2 possess a strong virucidal activity against SARS-CoV-2 in vitro and block the cell fusion mediated by spike glycoprotein interaction with the ACE2 receptor
Andrei E. Siniavin, Maria A. Nikiforova, Svetlana D. Grinkina, Vladimir A. Gushchin, Vladislav G. Starkov, Alexey V. Osipov, Victor I. Tsetlin, Yuri N. Utkin
bioRxiv 2021.01.12.426042; doi: https://doi.org/10.1101/2021.01.12.426042
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Snake venom phospholipases A2 possess a strong virucidal activity against SARS-CoV-2 in vitro and block the cell fusion mediated by spike glycoprotein interaction with the ACE2 receptor
Andrei E. Siniavin, Maria A. Nikiforova, Svetlana D. Grinkina, Vladimir A. Gushchin, Vladislav G. Starkov, Alexey V. Osipov, Victor I. Tsetlin, Yuri N. Utkin
bioRxiv 2021.01.12.426042; doi: https://doi.org/10.1101/2021.01.12.426042

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