ABSTRACT
BACKGROUND: The novel coronavirus disease-2019 (COVID-19) that emerged in China, is an extremely contagious and pathogenic viral infection caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that has sparked a global pandemic. The few and limited availability of approved therapeutic agents or vaccines is of great concern. Urgently, Remdesivir, Nirmatrelvir, Molnupiravir, and some phytochemicals including polyphenol, flavonoid, alkaloid, and triterpenoid are applied to develop as repurposing drugs against the SARS-CoV-2 invasion. METHODS: This study was conducted to perform molecular docking and absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis of the potential phytocompounds and repurposing drugs against three targets of SARS-CoV-2 proteins (RNA dependent RNA polymerase, RdRp, Endoribonclease, S-protein of ACE2-RBD). RESULTS: The docking data illustrated Arachidonic acid, Rutin, Quercetin, and Curcumin were highly bound with coronavirus polyprotein replicase and Ebolavirus envelope protein. Furthermore, anti- Ebolavirus molecule Remedesivir, anti-HIV molecule Chloroquine, and Darunavir were repurposed with coronavirus polyprotein replicase as well as Ebolavirus envelope protein. The strongest binding interaction of each targets are Rutin with RdRp, Endoribonclease with Amentoflavone, and ACE2-RBD with Epigallocatechin gallate. CONCLUSIONS: Taken altogether, these results shed a light on that phytocompounds have a therapeutic potential for the treatment of anti-SARS-CoV-2 may base on multi-target effects or cocktail formulation for blocking viral infection through invasion/activation, transcription/reproduction, and posttranslational cleavage to battle COVID-19 pandemic.
ABSTRACT
BACKGROUND: SARS-CoV-2, an emerged strain of corona virus family became almost serious health concern worldwide. Despite vaccines availability, reports suggest the occurrence of SARS-CoV-2 infection even in a vaccinated population. With frequent evolution and expected multiple COVID-19 waves, improved preventive, diagnostic, and treatment measures are required. In recent times, phytochemicals have gained attention due to their therapeutic characteristics and are suggested as alternative and complementary treatments for infectious diseases. This present study aimed to identify potential inhibitors against reported protein targets of SARS-CoV-2. METHODOLOGY: We computationally investigated potential SARS-CoV-2 protein targets from the literature and collected druggable phytochemicals from Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT) database. Further, we implemented a systematic workflow of molecular docking, dynamic simulations and generalized born surface area free-energy calculations (MM-GBSA). RESULTS: Extensive literature search and assessment of 1508 articles identifies 13 potential SARS-CoV-2 protein targets. We screened 501 druggable phytochemicals with proven biological activities. Analysis of 6513(501 *13) docked phytochemicals complex, 26 were efficient against SARS-CoV-2. Amongst, 4,8-dihydroxysesamin and arboreal from Gmelina arborea were ranked potential against most of the targets with binding energy ranging between - 10.7 to - 8.2 kcal/mol. Additionally, comparative docking with known drugs such as arbidol (-6.6 to -5.1 kcal/mol), favipiravir (-5.5 to -4.5 kcal/mol), hydroxychloroquine (-6.5 to -5.1 kcal/mol), and remedesivir (-8.0 to -5.3 kcal/mol) revealed equal/less affinity than 4,8-dihydroxysesamin and arboreal. Interestingly, the nucleocapsid target was found commonly inhibited by 4,8-dihydroxysesamin and arboreal. Molecular dynamic simulation and Molecular mechanics generalized born surface area (MM-GBSA)calculations reflect that both the compounds possess high inhibiting potential against SARS-CoV-2 including the recently emerged Omicron variant (B.1.1.529). CONCLUSION: Overall our study imparts the usage of phytochemicals as antiviral agents for SARS-CoV-2 infection. Additional in vitro and in vivo testing of these phytochemicals is required to confirm their potency.
ABSTRACT
Severe acute respiratory syndrome (SARS) develops within 3-14 days when CoV2 invades epithelial, myeloid cells in the nasopharynx and pneumocytes in the respiratory tract through angiotensin converting enzyme (ACE2). Infection swiftly disseminates to gastrointestinal, cardiovascular, renal organs as well as immune system to deregulate their normal functioning through unique and distinct mechanisms. The health system and economy has been intensely thwarted by the rapid spread and exorbitant mortality caused by COVID-19 disease across the globe. The acute progression of the disease and high infection rate pose an enormous challenge for its therapeutic management and critical care. The viral structure, genome and proteome have been deciphered which yielded cues for targeting already available therapeutic entities. More than 200 compounds have been screened and till date approximately 69 therapeutic agents are undergoing clinical trials across the world. Among these, remedesivir (RMD), chloroquine (CQ), hydroxychloroquine (HCQ), noscapine (NOS) and heparin have demonstrated fairly promising results in preclinical and clinical studies. Recently, RMD has been approved by USFDA for the management of COVID 19. However, intense research is going on to screen and ace the 'magic bullets' for the management of SARS-CoV2 infection worldwide. The current review illustrates the plausible therapeutic targets in SARS-CoV2 important for inhibition of virus cycle. In addition, the role of RMD, CQ, HCQ, NOS and heparin in combating infection has been addressed. The importance of vitamin C and D supplements as adjunct therapies in the prevention of SARS-CoV2 virus infection have also been summarized.