β-coronavirus (CoVs) alone has been responsible for three major global outbreaks in the 21st century. The current crisis has led to an urgent requirement to develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components are required as a backup against the emergence of lethal viral variants. One such target is the main protease (M pro ) that plays an indispensable role in viral replication. The availability of over 270 M pro X-ray structures in complex with inhibitors provides unique insights into ligand–protein interactions. Herein, we provide a comprehensive comparison of all nonredundant ligand-binding sites available for SARS-CoV2, SARS-CoV, and MERS-CoV M pro . Extensive adaptive sampling has been used to investigate structural conservation of ligand-binding sites using Markov state models (MSMs) and compare conformational dynamics employing convolutional variational auto-encoder-based deep learning. Our results indicate that not all ligand-binding sites are dynamically conserved despite high sequence and structural conservation across β-CoV homologs. This highlights the complexity in targeting all three M pro enzymes with a single pan inhibitor.

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β-coronaviruses alone have been responsible for three major global outbreaks in the 21st century. The current crisis has led to an urgent requirement to develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components are required as a back-up against the emergence of lethal viral variants. One such target is the main protease (Mpro) that plays an indispensible role in viral replication. The availability of over 270 Mpro X-ray structures in complex with inhibitors provides unique insights into ligand-protein interactions. Herein, we provide a comprehensive comparison of all non-redundant ligand-binding sites available for SARS-CoV2, SARS-CoV and MERS-CoV Mpro. Extensive adaptive sampling has been used to explore conformational dynamics employing convolutional variational auto encoder-based deep learning, and investigates structural conservation of the ligand binding sites using Markov state models across β-coronavirus homologs. Our results indicate that not all ligand-binding sites are dynamically conserved despite high sequence and structural conservation across β-coronavirus homologs. This highlights the complexity in targeting all three Mpro enzymes with a single pan inhibitor.

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Background: A prospective cross sectional study was designed to determine the prevalence rate of postpartum depression and its association with antenatal depression among women coming to the antenatal Clinic and birthing at HAHC Centenary Hospital, New Delhi. Material & Methods: 149 women by the assistance of EPDS (Hindi version) were screened at 6 weeks of their delivery. The participants were then divided on the basis of presence and absence of depression into two groups as depressed and non-depressed women. Results: 19 out 149 postnatal women scored ≥ 10 on EPDS which suggest the 12.75% prevalence rate of postnatal depression. Moreover 8(42.1 %) women among 19 depressed postnatal women and 25(19.3 %) women among 130 non-depressed postnatal women were found to have depression since their time of pregnancy thus a significant association (p-value= 0.025) was obtained. Conclusion: PPD is a major health problem in our community. Moreover, presence of depression during pregnancy significantly predisposes the postnatal mothers to be a victim of PPD. Therefore an early screening of the perinatal women is needed to unreveal the hidden cases as well as to prevent the mothers from the cruel penalties of PPD.