In silico prediction of the animal susceptibility and virtual screening of natural compounds against SARS-CoV-2: Molecular dynamics simulation based analysis.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. It has six open reading frames (orf1ab, orf3a, orf6, orf7a, orf8, and orf10), a spike protein, a membrane protein, an envelope small membrane protein, and a nucleocapsid protein, out of which, orf1ab is the largest ORF coding different important non-structural proteins. In this study, an effort was made to evaluate the susceptibility of different animals against SARS-CoV-2 by analyzing the interactions of Spike and ACE2 proteins of the animals and propose a list of potential natural compounds binding to orf1ab of SARS-CoV-2. Here, we analyzed structural interactions between spike proteins of SARS-CoV-2 and the ACE2 receptor of 16 different hosts. A simulation for 50 ns was performed on these complexes. Based on post-simulation analysis, Chelonia mydas was found to have a more stable complex, while Bubalus bubalis, Aquila chrysaetos chrysaetos, Crocodylus porosus, and Loxodonta africana were found to have the least stable complexes with more fluctuations than all other organisms. Apart from that, we performed domain assignment of orf1ab of SARS-CoV-2 and identified 14 distinct domains. Out of these, Domain 3 (DNA/RNA polymerases) was selected as a target, as it showed no similarities with host proteomes and was validated in silico. Then, the top 10 molecules were selected from the virtual screening of ∼1.8 lakh molecules from the ZINC database, based on binding energy, and validated for ADME and toxicological properties. Three molecules were selected and analyzed further. The structural analysis showed that these molecules were residing within the pocket of the receptor. Finally, a simulation for 200 ns was performed on complexes with three selected molecules. Based on post-simulation analysis (RMSD, RMSF, Rg, SASA, and energies), the molecule ZINC000103666966 was found as the most suitable inhibitory compound against Domain 3. As this is an in silico prediction, further experimental studies could unravel the potential of the proposed molecule against SARS-CoV-2.

Effect of restrictions imposed due to COVID-19 pandemic on the antenatal care and pregnancy outcomes: a prospective observational study from rural North India.

OBJECTIVES: To assess the difficulties faced by the pregnant women in seeking appropriate antenatal care due to the restrictions imposed during the COVID-19 pandemic; assess the difficulties encountered during delivery and postpartum period; the suitability of the teleconsultation services offered; effect of COVID-19 infection on pregnancy outcomes and the effect of restrictions on the nutrition profile of the pregnant women. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: We included 1374 pregnant women from the rural areas of three districts of Punjab, India registered at government health centres before the implementation of lockdown due to the COVID-19 pandemic on 24 March 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the difficulties faced by the women during their pregnancies due to restrictions imposed during the lockdown. The secondary outcomes included the effect of COVID-19 infections on pregnancy outcomes, satisfaction from the telemedicine services and restrictions on the nutrition profile of the pregnant women. RESULTS: One-third of the women (38.4%) considered their last pregnancy unplanned. Women faced difficulties due to the restrictions in getting adequate nutrition (76.5%), accessing transportation facilities (35.4%), consultations from doctors (22.4%) or getting an ultrasonography scan (48.7%). One-fifth (21.9%) of women could not access safe abortion services. Only 3.6% of respondents ever took any teleconsultation services offered by the government. Most of them felt unsatisfied compared with routine visits (77.5%). COVID-19-infected women were primarily asymptomatic (76.1%), but there was a high incidence of preterm birth (42.8%). Frontline workers could visit 64.3% of the women in the postpartum period despite restrictions. CONCLUSIONS: Lockdown compromised the antenatal care in our study area while the frontline workers attempted to minimise the inconvenience. Telemedicine services did not prove to be of many benefits to pregnant women and should only work as a supplement to the existing protocols of antenatal care.

SARS-CoV-2 Spike Glycoprotein and ACE2 Interaction Reveals Modulation of Viral Entry in Wild and Domestic Animals.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral pathogen causing life-threatening diseases in humans. Interaction between the spike protein of SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) is a potential factor in the infectivity of a host. In this study, the interaction of SARS-CoV-2 spike protein with its receptor, ACE2, in different hosts was evaluated to predict the probability of viral entry. Phylogeny and alignment comparison of the ACE2 sequences did not lead to any meaningful conclusion on viral entry in different hosts. The binding ability between ACE2 and the spike protein was assessed to delineate several spike binding parameters of ACE2. A significant difference between the known infected and uninfected species was observed for six parameters. However, these parameters did not specifically categorize the Orders into infected or uninfected. Finally, a logistic regression model constructed using spike binding parameters of ACE2, revealed that in the mammalian class, most of the species of Carnivores, Artiodactyls, Perissodactyls, Pholidota, and Primates had a high probability of viral entry. However, among the Proboscidea, African elephants had a low probability of viral entry. Among rodents, hamsters were highly probable for viral entry with rats and mice having a medium to low probability. Rabbits have a high probability of viral entry. In Birds, ducks have a very low probability, while chickens seemed to have medium probability and turkey showed the highest probability of viral entry. The findings prompt us to closely follow certain species of animals for determining pathogenic insult by SARS-CoV-2 and for determining their ability to act as a carrier and/or disseminator.