A pandemic caused by the novel coronavirus (SARS-CoV-2 or COVID-19) began in December 2019 in Wuhan, China, and the number of newly reported cases continues to increase. More than 19.7 million cases have been reported globally and about 728,000 have died as of this writing (10 August 2020). Recently, it has been confirmed that the SARS-CoV-2 main protease (Mpro) enzyme is responsible not only for viral reproduction but also impedes host immune responses. The Mpro provides a highly favorable pharmacological target for the discovery and design of inhibitors. Currently, no specific therapies are available, and investigations into the treatment of COVID-19 are lacking. Therefore, herein, we analyzed the bioactive phytocompounds isolated by gas chromatography–mass spectroscopy (GC-MS) from Tinospora crispa as potential COVID-19 Mpro inhibitors, using molecular docking study. Our analyses unveiled that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules, with three of them exerting biological activity and warranting further optimization and drug development to combat COVID-19.

AbstractBackgroundThe study investigated the in vivo neuroprotective, antinociceptive, anti-inflammatory potential and in vitro antioxidant and clot lysis activities of crude methanol extract with its different solvent-soluble fractions like petroleum ether (PESF), carbon tetrachloride (CTSF), chloroform (CSF) and aqueous (AQSF) of Holigarna longifolia Roxb.MethodsPhenobarbitone-induced sleeping time method was used for the neuroprotective activity, writhing response experimental model introduced by acetic acid was designed for antinociceptive efficacy, carrageenan-induced paw edema model was carried out for anti-inflammatory activity, DPPH free radical scavenging activity was assessed for antioxidant activity and clot lysis model was investigated for the thrombolytic potential of the plant.ResultsOn investigation it was found that methanol extract and CS fraction revealed statistically meaningful (p<0.05) neuroprotective activity by increasing phenobarbitone-induced sleeping time of mice, produced substantial (p<0.05) inflammation inhibitory efficacy compared to standard diclofenac sodium and also exhibited statistically significant (p<0.01) oxidative stress inhibitory efficacy by inhibiting free radical formation compared to ascorbic acid as standard. Only methanol extract produced significant (p<0.05) antinociceptive activity by inhibiting abdominal writhes produced by acetic acid compared to standard analgesic drug diclofenac sodium. And only aqueous soluble fraction exhibited moderate clot lysis activity compared to streptokinase as standard.ConclusionThe findings demonstrate that H. longifolia could be potential neuroprotective due to its justified antioxidative capacity as well as clot lysis properties.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first recognized in Wuhan in late 2019 and, since then, had spread globally, eventually culminating in the ongoing pandemic. As there is a lack of targeted therapeutics, there is certain opportunity for the scientific community to develop new drugs or vaccines against COVID-19 and so many synthetic bioactive compounds are undergoing clinical trials. In most of the countries, due to the broad therapeutic spectrum and minimal side effects, medicinal plants have been used widely throughout history as traditional healing remedy. Because of the unavailability of synthetic bioactive antiviral drugs, hence all possible efforts have been focused on the search for new drugs and alternative medicines from different herbal formulations. In recent times, it has been assured that the Mpro, also called 3CLpro, is the SARS-CoV-2 main protease enzyme responsible for viral reproduction and thereby impeding the host’s immune response. As such, Mpro represents a highly specified target for drugs capable of inhibitory action against coronavirus disease 2019 (COVID-19). As there continue to be no clear options for the treatment of COVID-19, the identification of potential candidates has become a necessity. The present investigation focuses on the in silico pharmacological activity of Calotropis gigantea, a large shrub, as a potential option for COVID-19 Mpro inhibition and includes an ADME/T profile analysis of that ligand. For this study, with the help of gas chromatography–mass spectrometry analysis of C. gigantea methanolic leaf extract, a total of 30 bioactive compounds were selected. Our analyses unveiled the top four options that might turn out to be prospective anti–SARS-CoV-2 lead molecules; these warrant further exploration as well as possible application in processes of drug development to combat COVID-19.