The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which was first reported in Wuhan province of China, has become a deadly pandemic causing alarmingly high morbidity and mortality. In the absence of new targeted drugs and vaccines against SARS-CoV-2 at present, the choices for effective treatments are limited. Therefore, considering the exigency of the situation, we focused on identifying the available approved drugs as potential inhibitor against the promising Coronavirus drug target, the Main Protease, using computer-aided methods. We created a library of U. S. Food and Drug Administration approved anti-microbial drugs and virtually screened it against the available crystal structures of Main Protease of the virus. The study revealed that Viomycin showed the highest -CDocker energy after docking at the active site of SARS-CoV-2 Main Protease. It is noteworthy that Viomycin showed higher -CDocker energy as compared to the drugs currently under clinical trial for SARS-CoV-2 treatment viz. Ritonavir and Lopinavir. Additionally, Viomycin formed higher number of H-bonds with SARS-CoV-2 Main Protease than its co-crystallised inhibitor compound N3. Molecular dynamics simulation further showed that Viomycin embedded deeply inside the binding pocket and formed robust binding with SARS-CoV-2 Main Protease. Therefore, we propose that Viomycin may act as a potential inhibitor of the Main Protease of SARS-CoV-2. Further optimisations with the drug may support the much-needed rapid response to mitigate the pandemic. Communicated by Ramaswamy H. Sarma

A new series of novel dipeptide sulfonamide analogues were designed, synthesized, and screened for their in silico studies and in vivo antimalarial activities. The synthesized compounds (50 mg/Kg) showed significant activity against P. berghei (NK65) with % inhibition values in (5.9 to 64.7 %) range in when compared with reference drug, artemisinin (66.7 %) in a four day suppressive assay. The in silico studies predicted favorable binding affinity of compounds with target protein residues with high dock score against P. falciparum falcipain 2 (FP‐2) and falcipain 3 (FP‐3) proteins in comparison with the reference ligands. The synthesized compounds showed druggable properties, and the predicted (absorption, distribution, metabolism, excretion and toxicities (ADMET) properties were within the acceptable limits. Molecular dynamics simulation study of the most active compound, 8 e was performed in order to further validate the stability of the protein‐ligand complex and the protein‐ligand interactions.

The high polarity of the protoberberine alkaloids present in Coptis teeta has made it difficult to quantify the alkaloids. This study was designed to develop and validate a thin-layer chromatography (TLC) densitometric-based method using high-performance thin-layer chromatography for quantification of berberine. The separation was achieved in a solvent system consisting of butanol:ethyl acetate:formic acid:water by volume on TLC aluminum plate precoated with silica gel 60 F254. Determination and quantification were performed by densitometric scanning under mercury lamp at a wavelength 351 nm in absorbance mode. The validated method gave compact bands for berberine at an Rf of 0.70. The precision, accuracy and reproducibility of the method were validated by following International Conference on Harmonization guidelines. Graphically, linear results were obtained for berberine with correlation coefficient of 0.997 ± 0.09% (R ± SD) in the concentration range of 90-210 ng/band. The limit of quantification and limit of detection from the analysis were found to be 70 and 30 ng/band, respectively. The berberine concentration in the methanol extract of C. teeta was found to be 30.97 ± 0.55 mg in 100 mg of the crude drug. The method developed here in can be implemented in the analysis and routine quality control of herbal materials and formulations containing C. teeta and berberine.

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in 2019 and is still an on-going pandemic. SARS-CoV-2 uses a human protease called furin to aid in cellular entry and its main protease (M^pro) to achieve viral replication. By targeting these proteins, scientists are trying to identify phytoconstituents of medicinal plants as potential therapeutics for COVID-19. Therefore, our study was aimed to identify promising leads as potential inhibitors of SARS-CoV-2 M^proand furin using the phytocompounds reported to be isolated fromAcacia pennata(L.) Willd.Results: A total of 29 phytocompounds were reported to be isolated fromA. pennata. Molecular docking simulation studies revealed 9 phytocompounds as having the top 5 binding affinities towards SARS-CoV-2 M^proand furin. Among these phytocompounds, quercetin-3-O-α-L-rhamnopyranoside (C_18), kaempferol 3-O-α-L-rhamnopyranosyl-(1 → 4)-β-D-glucopyranoside (C_4), and isovitexin (C_5) have the highest drug score. However, C_18 and C_4 were not selected for further studies due to bioavailability issues and low synthetic accessibility. Based on binding affinity, molecular properties, drug-likeness, toxicity parameters, ligand interactions, bioavailability, synthetic accessibility, structure–activity relationship, and comparative analysis of our experimental findings with other studies, C_5 was identified as the most promising phytocompound. C_5 interacted with the active site residues of SARS-CoV-2 M^pro(GLU166, ARG188, GLN189) and furin (ASN295, ARG298, HIS364, THR365). Many phytocompounds that interacted with these amino acid residues were reported by other studies as potential inhibitors of SARS-CoV-2 M^proand furin. The oxygen atom at position 18, the –OH group at position 19, and the 6-C-glucoside were identified as the pharmacophores in isovitexin (also known as apigenin-6-C-glucoside). Other in-silico studies reported apigenin as a potential inhibitor of SARS-CoV-2 M^proand apigenin-o-7-glucuronide was reported to show stable conformation during MD simulations with SARS-CoV-2 M^pro.Conclusion: The present study found isovitexin as the most promising phytocompound to potentially inhibit the cellular entry and viral replication of SARS-CoV-2. We also conclude that compounds having oxygen atom at position 18 (C-ring), –OH group at position 19 (A-ring), and 6-C-glucoside attached to the A-ring at position 3 on a C₆–C₃–C₆flavonoid scaffold could offer the best alternative to develop new leads against SARS-CoV-2.

Background: Development of resistance by the malaria parasite Plasmodium falciparum has created challenges in the eradication of this deadly infectious disease. Hence newer strategies are adopted to combat this disease and simultaneously, new lead/hit identification is going on worldwide to develop new chemotherapeutic agents against malaria. Objective: In this study, 44 flavonoids found mainly in the fruit juice of Citrus species having traditional use in malaria-associated fever were selected for in silico multiple-target directed screening against three vital targets of the parasite namely dihydroorotate dehydrogenase (PfDHODH), dihydrofolate reductase thymidine synthase (PfDHFR-TS) and plasma membrane P-type cation translocating ATPase (PfATP4) to find out new lead molecule(s). Methods: The in silico screening was carried out using different protocols of the Biovia Discovery Studio 2018 software and Network analyzer plugin of Cytoscape 3.6.0 followed by in vitro screening of the best lead. Results: After screening, CF8 or luteolin was found to have good binding affinity against PfDHODH and PfATP4 with –CDocker energy 42.2719 and 33.1447 with respect to their cocrystal ligands. These findings were also supported by structure-based pharmacophore, DFT (Density Functional Theory) study and finally by in vitro screening of the lead with IC50 values of 8.23 μm and 12.41 μm against 3D7 (chloroquine-sensitive) and RKL-9 (chloroquine-resistant) strain of P. falciparum, respectively. Conclusion: Our study found a moderately active lead molecule with the predicted mode of action which can be utilized to design some new derivatives with more safety and efficacy by targeting the two enzymes.

Substantial research is currently conducted focusing on the development of promising antiviral drugs employing in silico screening and drug repurposing strategies against SARS-CoV-2. The current study aims at identifying lead molecules targeting SARS-CoV-2 by the application of in silico and molecular dynamics (MD) approaches from phytoconstituents present in Homalomena aromatica. The main protease (M^pro) enzyme of SARS-CoV-2 is taken as the target protein to perform the docking analysis of 71 molecules reported from H. aromatica by the application of different modules of Discovery Studio 2018. Five molecules were taken as prospective leads namely dihydrocuminaldehyde, p-cymen-8-ol, cuminaldehyde, p-cymene, and cuminol. In the absence of known inhibitors, a comparative study was performed with the compounds reported in the literature and potent terpenoid–metal complexes were taken into account based on known efficacy as anti-viral molecules. After performing the docking studies with Mpro enzyme of SARS-CoV-2, it was observed that the –CDocker Energy of cuminaldehyde thiosemicarbazone was 29.152, indicating a significant affinity toward Mpro. The same was also supported by the MD study. Taken together, our results provided in silico evidence that secondary metabolites derived from H. aromatica could be employed as potent antiviral agents targeting SARS-CoV-2. Our findings warrant further validation of their in vitro and in vivo efficacies prior to their development into bona fide therapeutic agents.