In silico studies evidenced the role of structurally diverse plant secondary metabolites in reducing SARS-CoV-2 pathogenesis

Abstract

Plants are endowed with a large pool of structurally diverse small molecules known as secondary metabolites. The present study aims to virtually screen these plant secondary metabolites (PSM) for their possible anti-SARS-CoV-2 properties targeting four proteins/ enzymes which govern viral pathogenesis. Results of molecular docking with 4,704 ligands against four target proteins, and data analysis revealed a unique pattern of structurally similar PSM interacting with the target proteins. Among the top-ranked PSM which recorded lower binding energy (BE), > 50% were triterpenoids which interacted strongly with viral spike protein—receptor binding domain, > 32% molecules which showed better interaction with the active site of human transmembrane serine protease were belongs to flavonoids and their glycosides, > 16% of flavonol glycosides and > 16% anthocyanidins recorded lower BE against active site of viral main protease and > 13% flavonol glycoside strongly interacted with active site of viral RNA-dependent RNA polymerase. The primary concern about these PSM is their bioavailability. However, several PSM recorded higher bioavailability score and found fulfilling most of the drug-likeness characters as per Lipinski's rule (Coagulin K, Kamalachalcone C, Ginkgetin, Isoginkgetin, 3,3′-Biplumbagin, Chrysophanein, Aromoline, etc.). Natural occurrence, bio-transformation, bioavailability of selected PSM and their interaction with the target site of selected proteins were discussed in detail. Present study provides a platform for researchers to explore the possible use of selected PSM to prevent/ cure the COVID-19 by subjecting them for thorough in vitro and in vivo evaluation for the capabilities to interfering with the process of viral host cell recognition, entry and replication.

Natural product remedies for COVID-19: A focus on safety

“…Researchers have suggested that any therapeutic of interest should be able to show a high affinity to binding and inhibiting the SARS-CoV-2 spike protein, main protease enzyme (Mpro) and RdRp which are associated with host attachment and viral replication, resulting in infection in the individual. This has been demonstrated through in silico studies which is a quick way to identifying potential drugs ( Table 1 ) (e.g Kar et al, 2020 ; Puttaswamy et al, 2020 ). The SARS-CoV-2 spike protein is known to attach itself to the human receptor ACE2 through the receptor binding domain (RBD), and this enables viral entry in host cells causing a breakdown in the system of the host (Tai et al, 2020).…”

“…Hence extensive studies should be carried out on this phytocompound for the possible development of therapeutic against COVID-19. In another molecular docking study, Puttaswamy et al (2020) evaluated 4,704 ligands against four target proteins: Spike, RdRp, Mpro and the Human TMPRSS2 priming the SARS-CoV-2 spike protein. Authors observed a unique pattern of structurally similar interaction of some phytochemicals with the target proteins.…”

“…Arg. Euphorbiaceae − 8.8 Puttaswamy et al (2020) Pseudojervine Veratrum album L. Melanthiaceae − 8.7 Puttaswamy et al (2020) Flavin adenine dinucleotide NA − 8.6 Puttaswamy et al (2020) Graecunin E Trigonella foenum-graecum L. Fabaceae − 8.6 Puttaswamy et al (2020) Taraxerol Clerodendrum trichotomum Thunb. Lamiaceae -7.5 Kar et al (2020 a) Friedelin Clerodendrum trichotomum Thunb.…”

“…C. B. Clarke Gentianaceae -7.5 Kar et al (2020) Beta-amyrin Swertia chirata (Wall.) C. B. Clarke -7.1 Kar et al (2020) Glycyrrhizic acid Glycyrrhiza glabra L. Fabaceae − 9.5 Puttaswamy et al (2020) cis-Miyabenol C Foeniculum vulgare Mill. (fennel).…”

“… Apiacae − 9.4 Puttaswamy et al (2020) Proanthocyanidin A2 NA NA − 9.2 Puttaswamy et al (2020) Granatin B Punica granatum L. Punicaceae − 9.1 Puttaswamy et al (2020) Hippophaenin B NA NA − 9.1 Puttaswamy et al (2020) 3-Caffeoyl-5-Feruloylquinic Acid NA NA -9.0 Puttaswamy et al (2020) TMPRSS2 3,3′-Biplumbagin NA NA -8.9 Puttaswamy et al (2020) Agathisflavone NA NA -8.9 Puttaswamy et al (2020) Aromoline NA NA -8.9 Puttaswamy et al (2020) Chrysophanein NA NA -8.9 Puttaswamy et al (2020) RdRp Eriodictyol-7-O-rutinoside Citrus limon (L.) BURM.f. Rutaceae -9.9 Puttaswamy et al (2020) Narirutin NA NA -9.7 Puttaswamy et al (2020) Hippomannin A NA NA -9.6 Puttaswamy et al (2020) Isoginkgetin Ginkgo biloba L. Ginkgoaceae -9.5 Puttaswamy et al (2020) Kaempferol 3-O-(6′’-galloyl)-beta-D-glucopyranoside …”