Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the current global pandemic that has caused a death toll of >1.12 million worldwide and number continues to climb in several countries. Currently, there are neither specific antiviral drugs nor vaccines for the treatment and prevention of COVID-19. We screened in silico, a group of natural spice and herbal secondary metabolites (SMs) for their inhibition efficacy against multiple target proteins of SARS-CoV-2 as well as the human angiotensin-converting enzyme 2 protein. Docking and simulation results indicated that epicatechin, embelin, hesperidin, cafestol, murrayanine and murrayaquinone-A have higher inhibition efficacy over at least one of the known antiviral drugs such as Hydroxychloroquine, Remdesivir and Ribavirin. Combination of these potentially effective SMs from their respective plant sources was analysed, and its absorption and acute oral toxicity were examined in Wistar rats and classified as category 5 as per the Globally Harmonized System. The identified SMs may be useful in the development of preventive nutraceuticals, food supplements and antiviral drugs. Communicated by Ramaswamy H. Sarma Graphical Abstract

Protein phosphorylation is an important mechanism that implicates in physiology of any organism including parasitic protozoa. Metallic protein Ser/Thr protein phosphatase 5 (PP5) controls various cellular signaling pathways of Plasmodium falciparum. The structure and inhibitory mechanism of PP5 in P. falciparum is not known. In fact, no experimental structural data are available for P. falciparum Ser/Thr protein phosphatase 5 (PfPP5) till date. Hence, we have proposed computer-generated model of catalytic subunit of PfPP5 and its inhibitory mechanism was analyzed. A set of 42 known natural inhibitors of protein phosphate family were docked against metal-binding catalytic site of PfPP5 and we found that cantharidin and its derivatives shows better binding energy among them. Similarity search was performed by taking these compounds as lead compounds against PubChem and ChemBank. The search result provides 3703 similar compounds; out of which 2245 qualified the Lipinski rule of five. Further, virtual screening of these compounds was performed and selected top 25 were selected on the basis of binding energy. In continuation, rigid and flexible docking of these screened compounds was performed to get the insight of interactions. Finally, top 5 compounds were verified for ADMET properties, and then, all are subjected to MD simulations for 25 ns in order to validate their stability. Compounds CBI: 3554182, CID: 23561913, and CID: 21168680 showed most stable binding, although some of hydrogen bonds pairing varied throughout simulation. These finding would be helpful to the medicinal chemists for the development of antimalarial drugs to combat this deadly disease.

World-wide grown and consumed tomato (Solanum lycopersicum) crop used as model system for new cultivar and fruit development. Genetic and genomic research of Indian tomato cultivars will provide an insight to develop new breeding strategies and crop improvement. The present study aimed to identify the high quality common and unique single nucleotide polymorphisms (SNPs), present in 9 different Indian tomato cultivars using double digestion restriction associated DNA sequencing (ddRAD-seq). Total of 36,847,092 raw reads (3.68 GB) were generated for all samples and 3,329,625 of high-quality reads were aligned uniquely to the reference tomato genome. Using stringent filtering, a total of 1,165 SNPs and 69 INDELs were found in genic regions, along with the unique variants to each cultivar was observed. Similarly, 7 and 33 variants were identified in chloroplast and mitochondrial genome of tomato. In addition, the population structure and genetic relationship among these cultivars suggested 4 well-differentiated sub-populations. Functional annotation of SNP/INDLEs associated with flanking sequences along with gene ontology and pathway analysis was performed. Identified SNPs/INDELs could be useful as markers for variety identification for genetic purity analysis. Findings from this work will be useful to plant breeders and research community to deepen their understanding and enhance tomato breeding programs.