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Coronavirus disease-2019 (COVID-19) is a highly contagious acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with its source first reported in the city of Wuhan, China (Keretsu et al., 2020; Pal et al., 2020). SARS-CoV2 is a positive-stranded RNA virus with a crown-shaped appearance on the surface and is very minute in size, 65–125nm diameter (Abdelmageed et al., 2020; Shereen et al., 2020). It is a highly contagious virus that can spread via droplets and aerosols breath out from the infected individuals through breathing, speaking, sneezing, or coughing (Prather, 2020; Zhang, 2020). The main symptoms of COVID-19 are fever, coughing, shortness of breath, congestion/runny nose, nausea, fatigue, body aches, headache, sore throat, loss of smell or taste, and diarrhea (Kousar et al., 2020).
Spike proteins, RNA-dependent RNA polymerase (RdRp), envelope proteins, membrane proteins, nucleocapsid proteins, and non-structural proteins are the major proteins involved in the pathogenesis of SARS-CoV-2. Their functions include receptor recognition, cell membrane fusion process, promoting replication, transmission, host cell interaction of the virus, etc (Huang et al., 2020; Skariyachan et al., 2020; Thomas 2020). Spike proteins are the major antigen for the vaccine design as they can induce neutralizing antibodies and protective immunity (Khalaj & Hedayati 2020). RdRp is another promising drug target of SARS-CoV-2. It is a viral enzyme with no host cell homologs and is involved in the viral RNA replication in host cells (Zhu et al., 2020). Proteases of SARS-CoV-2 include 3CLpro and PLpro. The 3-chymotrypsin-like cysteine protease (3CLpro) is the main protease in coronavirus that performs viral replication and polyprotein processing. 3CLpro is already a proven drug target for SARS and MERS-CoVs (Mandal et al., 2021). The papain-like protease (PLpro) is needed to generate a functional replicase complex and performs viral replication and immune evasion (Shin et al., 2020). It is involved in the processing of the viral polyprotein (Gao et al., 2020). Studies have shown that any conformational change or damage to the SARS-CoV proteins (especially spike proteins, RdRp, and proteases) might inactivate the virus thereby decreasing its virulence (Darnell et al., 2004). Thus, the four groups of proteins - Spike, RdRp, 3CLpro, and PLpro involving pathogenesis of SARS-CoV-2 were considered as targets for the study.
Plants and phyto compounds have long been propitious substitutes in the treatment of several diseases. They possess favorable potency and bearable toxicity. Various studies have been conducted to prove the effectiveness of plants in the treatment of COVID-19 (Benarba & Pandiella, 2020). Some phyto compounds were reported to have potent antiviral properties and are used in clinical trials (Huang et al., 2020). In silico methods help in drug designing for COVID-19, as it is rapid and cost-effective compared to the trial and error methods using clinical experimental analysis. This study mainly focuses on the in silico analysis of phyto compounds against the multiple targets of SARS-CoV2. Ten newly modeled small molecules were also considered as ligands for the study. Molecular docking analysis and molecular dynamics simulations were performed to understand and validate the protein-ligand interactions.