In Silico Mutagenesis-Based Remodelling of SARS-CoV-1 Peptide (ATLQAIAS) to Inhibit SARS-CoV-2: Structural-Dynamics and Free Energy Calculations.

The prolific spread of COVID-19 caused by a novel coronavirus (SARS-CoV-2) from its epicenter in Wuhan, China, to every nook and cranny of the world after December 2019, jeopardize the prevailing health system in the world and has raised serious concerns about human safety. Multi-directional efforts are made to design small molecule inhibitors, and vaccines and many other therapeutic options are practiced, but their final therapeutic potential is still to be tested. Using the old drug or vaccine or peptides could aid this process to avoid such long experimental procedures. Hence, here, we have repurposed a small peptide (ATLQAIAS) from the previous study, which reported the inhibitory effects of this peptide. We used in silico mutagenesis approach to design more peptides from the native wild peptide, which revealed that substitutions (T2W, T2Y, L3R, and A5W) could increase the binding affinity of the peptide towards the 3CLpro. Furthermore, using MD simulation and free energy calculation confirmed its dynamics stability and stronger binding affinities. Per-residue energy decomposition analysis revealed that the specified substitution significantly increased the binding affinity at the residue level. Our wide-ranging analyses of binding affinities disclosed that our designed peptide owns the potential to hinder the SARS-CoV-2 and will reduce the progression of SARS-CoV-2-borne pneumonia. Our research strongly suggests the experimental and clinical validation of these peptides to curtail the recent corona outbreak.

Ethnobotanical survey of the medicinal flora of Harighal, Azad Jammu & Kashmir, Pakistan.

BACKGROUND: The present study is the first quantitative ethnobotanical evaluation of Harighal, an inaccessible and unexplored area of District Bagh Azad Jammu & Kashmir (AJK). The exploration, quantification, and comparison of ethnobotanical knowledge among different rural communities of the study area were mainly focused during field survey. METHODOLOGY: In total, 79 informants (49 men and 34 women) were selected randomly to collect data using a semi-structured questionnaire. Various quantitative indices, including use value, relative frequency of citation, relative importance, fidelity level, and informant consent factor, were employed to evaluate the gathered information. Furthermore, primary data were also compared with twenty-two papers published from adjoining areas. RESULT: A total of 150 medicinal plants belonging to 98 genera and 60 families were documented. Asteraceae, Fabaceae, and Rosaceae were the dominant families having 15 species each. Of these, 76 species were indigenous, 74 exotic, 136 were collected in the wild, 10 cultivated, and 4 both wild-collected and cultivated. Herbaceous taxa were the most used life form, and leaves were the most exploited plant part. Decoctions were the most preferred method used in preparation of herbal recipes. Three species viz. Mentha longifolia, Berberis lycium, and Galium aparine had the highest use value (1.05), relative frequency of citation (0.81), and relative importance value (96), respectively. The highest informant consensus factor (ICF) was reported for digestive disorders. Mentha longifolia, Punica granatum, Zanthoxylum alatum, and Olea ferruginea had 100% fidelity values. The Jaccard index revealed that uses of plants were more similar in two neighboring areas, i.e., Pearl Valley and Toli Peer. CONCLUSION: Local inhabitants still prioritize herbal medicines as an effective way to treat a wide variety of ailments. Elders and health practitioners of the study area are well aware of indigenous knowledge about medicinal plants, but young people are not much interested in herbal practices. Thus, valuable knowledge about the use of plants is on the verge of decline.