The spread of novel coronavirus SARS-CoV-2 has directed to a state of an unprecedented global pandemic. Many synthetic compounds and FDA-approved drugs have been significantly inhibitory against the virus, but no SARS-CoV-2 solution has been identified. However, small molecule fragment–based derivatives of potent phytocompounds may serve as promising inhibitors against SARS-CoV-2. In the pursuit of exploring novel SARS-CoV-2 inhibitors, we generated small molecule fragment derivatives from potent phytocompounds using neural networking and machine learning–based tools, which can cover unexplored regions of the chemical space that still retain lead-like properties. Out of 300 derivative molecules from withaferin-A, hesperidin, and baicalin, 30 were screened out with synthetic accessibility scores > 4 having the best ADME properties. The withaferin-A derivative molecules 61 and 64 exhibited a significant binding affinity of − 7.84 kcal/mol and − 7.94 kcal/mol. The docking study reveals that withaferin-A mol 61 forms 5 polar H-bonds with the M pro where amino acids involved are GLU166, THR190, CYS145, MET165, and GLN152 and upon QSAR analysis showed a minimal predicted IC50 value of 7762.47 nM. Furthermore, the in silico cytotoxicity predictions, pharmacophore modeling, and molecular dynamics simulation studies have resulted in predicting the highly potent small molecule derivative from withaferin-A (phytocompound from Withania somnifera ) to be the potential inhibitor of SARS-CoV 2 protease (M pro ) and a promising future lead candidate against COVID-19. The rationale of choosing withaferin-A from Withania somnifera (Ashwagandha) was propelled by the innumerous applications of Ashwagandha for the treatment of various antiviral diseases, common cold, and fever since time immemorial. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00894-021-04703-6.

We wished to determine whether rare diseases patients from India had been enrolled in international trials to develop novel orphan drugs. There are two reasons to be interested in this. (a) Different ethnic or racial groups may respond differently to a particular drug. India has huge ethnic diversity, and to exclude such participants is to severely limit the diversity of any trial; (b) Even if a suitable drug for a rare disease is available in India, it may be astronomically priced, in a country where most healthcare expenditure is out-of-pocket. We identified 63 orphan drugs, approved by the US Food and Drug Administration (FDA) after 2008, for which there were 202 trials in the US government’s clinical trial registry, ClinicalTrials.gov. Only nine of these trials had run in India. These trials pertained to six drugs. The drugs were for the conditions B-cell Lymphoma, Chronic Myeloid Leukemia, Gaucher disease Type 1, Malaria, Myeloma and Pulmonary Arterial Hypertension. Further research is required as to why patients from India are not part of foreign drug development programmes for rare diseases. We then asked how many of the remaining 193 trials had recruited people of Indian origin, residing in other countries, and found that not more than 1% of these trials had done so. Also, only 11 of the 193 trials had recruited from other lower income countries. Participation from low-income countries in trials for orphan drugs is poor.

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Plants, upon exposure to environmental stress, express sophisticated and co-ordinated responses to reprogram interconnected defense networks and metabolic pathways. These responses are governed by intricate molecular and biochemical signal transduction processes, which act in harmonization to determine tolerance and sensitivity at a holistic level. Modern studies in plant stress biology include identification of key genes that influence stress tolerance and the verification of gene functions using knockout mutants or over-expression lines. Abiotic stresses induce aberrant expression of many miRNAs, suggesting that miRNAs could be a new target for genetically improving plant stress tolerance. MicroRNAs (miRNAs), 21-24 nts in length, are an extensive class of endogenous small RNA molecules that provide a fascinating option for engineering tolerance to environmental stress by serving as non-protein coding switches of both desirable and undesirable gene expressions. During abiotic stress, miRNAs function by regulating target genes within the stress regulated networks like signalling components and a variety of transcription factors (TFs). It is important to identify the expression domains of miRs and their targets to understand how the spatio-temporal regulations are co-ordinated under stress. In this project, we aim to design reporter gene construct containing the target site of selected miR. We have selected pCAMBIA1302 vector with aim to insert the target site before the ATG of GFP gene such that the coding frame remains intact. Later, the functionality of the designed construct can be checked by expressing the constructs In planta using Agroinfiltration and the technology is expected to greatly favour in molecular pharming.