Discovery of putative inhibitors against main drivers of SARS-CoV-2 infection: Insight from quantum mechanical evaluation and molecular modeling.

SARS-CoV-2 triggered a worldwide medical crisis, affecting the world's social, emotional, physical, and economic equilibrium. However, treatment choices and targets for finding a solution to COVID-19's threat are becoming limited. A viable approach to combating the threat of COVID-19 is by unraveling newer pharmacological and therapeutic targets pertinent in the viral survival and adaptive mechanisms within the host biological milieu which in turn provides the opportunity to discover promising inhibitors against COVID-19. Therefore, using high-throughput virtual screening, manually curated compounds library from some medicinal plants were screened against four main drivers of SARS-CoV-2 (spike glycoprotein, PLpro, 3CLpro, and RdRp). In addition, molecular docking, Prime MM/GBSA (molecular mechanics/generalized Born surface area) analysis, molecular dynamics (MD) simulation, and drug-likeness screening were performed to identify potential phytodrugs candidates for COVID-19 treatment. In support of these approaches, we used a series of computational modeling approaches to develop therapeutic agents against COVID-19. Out of the screened compounds against the selected SARS-CoV-2 therapeutic targets, only compounds with no violations of Lipinski's rule of five and high binding affinity were considered as potential anti-COVID-19 drugs. However, lonchocarpol A, diplacol, and broussonol E (lead compounds) were recorded as the best compounds that satisfied this requirement, and they demonstrated their highest binding affinity against 3CLpro. Therefore, the 3CLpro target and the three lead compounds were selected for further analysis. Through protein-ligand mapping and interaction profiling, the three lead compounds formed essential interactions such as hydrogen bonds and hydrophobic interactions with amino acid residues at the binding pocket of 3CLpro. The key amino acid residues at the 3CLpro active site participating in the hydrophobic and polar inter/intra molecular interaction were TYR54, PRO52, CYS44, MET49, MET165, CYS145, HIS41, THR26, THR25, GLN189, and THR190. The compounds demonstrated stable protein-ligand complexes in the active site of the target (3CLpro) over a 100 ns simulation period with stable protein-ligand trajectories. Drug-likeness screening shows that the compounds are druggable molecules, and the toxicity descriptors established that the compounds demonstrated a good biosafety profile. Furthermore, the compounds were chemically reactive with promising molecular electron potential properties. Collectively, we propose that the discovered lead compounds may open the way for establishing phytodrugs to manage COVID-19 pandemics and new chemical libraries to prevent COVID-19 entry into the host based on the findings of this computational investigation.

Discovery of Promising Inhibitors for SARS-CoV-2 Therapeutic Targets: A Quantum Mechanics and Molecular Modeling study (preprint)

SARS-CoV-2 triggers a worldwide medical crisis, affecting the world's social, emotional, physical, and economic equilibrium. However, treatment choices and targets for finding a solution to COVID-19's threat are becoming limiting. A viable approach to combating the threat of COVID-19 is to create pharmacological and therapeutic targets by uncovering promising inhibitors and proteins in the viral life cycle of COVID-19. Therefore, in this study, we employ high-throughput virtual screening to screen library of phytocompounds from selected medicinal plants targeting SARS-CoV-2 spike glycoprotein, 3CLpro, PLpro and RdRp. Virtual screening approach have been reported as a promising method to identify biologically active compounds from large libraries. In addition, molecular docking, Prime MM/GBSA (molecular mechanics/generalized born surface area) analysis, molecular dynamics (MD) simulation and pharmacokinetic/drug-likeness model was performed to identify potential phytodrugs. In support to these approaches, we employ series of chemical quantum calculation, semi empirical Hamiltonian and density functional theory analysis to develop therapeutic agents against COVID-19. We propose that the discover therapeutic targets/molecules may open the way for the establishment of phytodrugs for the management of COVID-19 pandemics and new chemical libraries for preventing COVID-19 entry into the host, based on the findings of this integrated computational investigation.

COVID-19 clinical presentations: the modern mimic of other conditions

The coronavirus pandemic (COVID-19) has placed enormous challenges on the health sector. Diagnosis is one of these challenges, where a clinical presentation may suggest a disease other than COVID-19. In this review we describe many presentations unrelated to the respiratory system. The ACE2 receptor is present in a wide variety of body tissues and it appears that this may be a link with the clinical pathology. To find these data we searched the major academic research engines, Google Scholar, and Pubmed, as well as the most recent case reports and original research published in specialized journals.

Repositioning gastroenterology services during covid-19 pandemic

BACKGROUND: In COVID-19 pandemic, hospitals become overwhelmed with acute admissions leading to the suspension of outpatient clinics including gastroenterology and endoscopic services. Similarly available resources are channeled to combat the scourge. These diversions of resources coupled with lockdowns and fear of getting infected prevent patients from accessing routine and lifesaving gastroenterology services leading to increased gastrointestinal-related morbidity and mortality in at-risk populations. Often, there are delays in the diagnosis and early treatment of gastrointestinal cancers, and high risks of death from gastrointestinal bleeding. SUMMARY: This review discusses COVID-19 risk factors and ways and means of ensuring safe essential gastroenterology services in the setting of COVID-19 pandemic based on available evidence. Telemedicine avoids physical contacts, maximizes safety by reducing the risk of infection to both clinicians and patients, and is conducive to a lockdown, quarantine, or self-isolation environment of COVID-19. It can be used to triage critical cases requiring life-saving endoscopic procedures. The review also explores measures at derisking endoscopies being high-risk aerosol generating procedures. The emerging technology of non-contact endoscopy in the form of robotic endoscopy raises hope in this direction.