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Letters in Drug Design & Discovery

Author(s): Linda Benincasa, Eleonora Molesti, Alessandro Manenti, Emanuele Montomoli, Alessio Malacrida, Valentina Zuliani, Mirko Rivara*, Gabriella Nicolini and Alessandro Di Domizio

DOI: 10.2174/1570180819666220701105250

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Potential In-vitro Antiviral Activity of MV1035 on SARS-CoV-2 Wild Type Viruses

Page: [1656 - 1663] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a positive- sense, single stranded RNA virus, responsible for the pandemic outbreak called COVID-19. The pandemic, still ongoing, had presented unprecedented challenges in terms of finding appropriate pharmacological treatments.

Methods: Starting from the recent literature that demonstrates how ALKBH5 inhibitors could be used as a new strategy to reduce SARS-CoV-2 replication, we decided to repurpose our newly discovered ALKBH5 inhibitor MV1035, previously tested and proved effective against glioblastoma, for its putative antiviral activity against SARS-CoV-2. We demonstrated a reduction in SARS-CoV- 2-induced CPE after 72 h incubation using MV1035 (50 μM), for SARS-CoV-2 wild type (Wuhan strain) and South African variant.

Results: The results show how MV1035 seems to be able to reduce SARS-CoV-2 replication through an indirect mechanism of action, which might involve an interaction with the host cell rather than with a virus protein.

Conclusion: This may be particularly interesting as it lays the foundation for the rational design of molecules in principle not subject to drug resistance, as host cell proteins are not affected by virus mutations.

Keywords: SARS-CoV-2, ALKBH5, antiviral

Graphical Abstract

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