Natural Products with Tandem Anti-inflammatory, Immunomodulatory
and Anti-SARS-CoV/2 Effects: A Drug Discovery Perspective
against SARS-CoV-2

Luana   N.O. Leal   da Cunha; Tiago      Tizziani; Gabriella   B.   Souza; Monalisa    A.   Moreira; José   S.S.   Neto; Carlos   V.D.   dos Santos; Maryelle   G.   de Carvalho; Eduardo    M.   Dalmarco; Leonardo   B.   Turqueti; Marcus   Tullius   Scotti; Luciana      Scotti; Francisco    F.   de Assis; Antonio   Luiz   Braga; Louis   Pergaud   Sandjo
Abstract

Background: COVID-19 is still causing long-term health consequences, mass deaths, and collapsing healthcare systems around the world. There are no efficient drugs for its treatment. However, previous studies revealed that SARS-CoV-2 and SARS-CoV have 96% and 86.5% similarities in cysteine proteases (3CL^pro) and papain-like protease (PL^pro) sequences, respectively. This resemblance could be important in the search for drug candidates with antiviral effects against SARS-CoV-2.
Objective: This paper is a compilation of natural products that inhibit SARS-CoV 3CL^pro and PL^pro and, concomitantly, reduce inflammation and/or modulate the immune system as a perspective strategy for COVID-19 drug discovery. It also presents in silico studies performed on these selected natural products using SARS-CoV-2 3CL^pro and PL^pro as targets to propose a list of hit compounds.
Methods: The plant metabolites were selected in the literature based on their biological activities on SARS-CoV proteins, inflammatory mediators, and immune response. The consensus docking analysis was performed using four different packages.
Results: Seventy-nine compounds reported in the literature with inhibitory effects on SARS-CoV proteins were reported as anti-inflammatory agents. Fourteen of them showed immunomodulatory effects in previous studies. Five and six of these compounds showed significant in silico consensus as drug candidates that can inhibit PL^pro and 3CL^pro, respectively. Our findings corroborated recent results reported on anti-SARS-CoV-2 in the literature.
Conclusion: This study revealed that amentoflavone, rubranoside B, savinin, psoralidin, hirsutenone, and papyriflavonol A are good drug candidates for the search of antibiotics against COVID-19.
Keywords: Natural products, COVID-19, 3CL^pro and PL^pro inhibitory effect, anti-inflammatory effect, immunomodulatory effect, drug discovery.
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Cite As
Current Medicinal Chemistry

Natural Products with Tandem Anti-inflammatory, Immunomodulatory and Anti-SARS-CoV/2 Effects: A Drug Discovery Perspective against SARS-CoV-2

Abstract
