Computational investigation reveals that the mutant strains of SARS-CoV2 have differential structural and binding properties.

BACKGROUND AND OBJECTIVES: Remarkable infectivity of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) is due to the rapid emergence of various strains which enable the virus to ruling the world. Over the course of SARS-CoV2 pandemic, the scientific communities worldwide are responding to newly emerging genetic variants. However, mechanism behind the persistent infection of these variants is still not known due to the paucity of study of these variants at molecular level. In this scenario, computational methods have immense utility in understanding the molecular and functional properties of different variants. METHODS: The various mutants (MTs) of SpikeS1 receptor binding domain (RBD) of highly infectious SARS-CoV2 strains were manifested and elucidated the protein structure and binding strength using molecular dynamics (MD) simulation and protein-protein docking approaches. RESULTS: MD simulation study showed that all MTs exhibited stable structures with altered functional properties. Furthermore, the binding strength of different MTs along with WT (wildtype) was revealed that MTs showed differential binding affinities to host protein with high binding strength exhibited by V367F and V483A MTs. CONCLUSION: Hence, this study shed light on the molecular basis of infection caused by different variants of SARS-CoV2, which might play an important role in to cease the transmission and pathogenesis of virus and also implicate in rational designing of a specific drug.

Immunological Mechanisms of Vaccine-Induced Protection against SARS-CoV-2 in Humans

The SARS-CoV-2 infection spread rapidly throughout the world and appears to involve in both humoral and cell-mediated immunity. SARS-CoV-2 is attached to host cells via binding to the viral spike (S) proteins and its cellular receptors angiotensin-converting enzyme 2 (ACE2). Consequently, the S protein is primed with serine proteases TMPRSS2 and TMPRSS4, which facilitate the fusion of viral and cellular membranes result in the entry of viral RNA into the host cell. Vaccines are urgently required to combat the coronavirus disease 2019 (COVID-19) outbreak and aid in the recovery to pre-pandemic levels of normality. The long-term protective immunity is provided by the vaccine antigen (or pathogen)-specific immune effectors and the activation of immune memory cells that can be efficiently and rapidly reactivated upon pathogen exposure. Research efforts aimed towards the design and development of vaccines for SARS-CoV-2 are increasing. Numerous coronavirus disease 2019 (COVID-19) vaccines have passed late-stage clinical investigations with promising outcomes. This review focuses on the present state and future prospects of COVID-19 vaccines research and development, with a particular emphasis on immunological mechanisms of various COVID-19vaccines such as adenoviral vector-based vaccines, mRNA vaccines, and DNA vaccines that elicits immunological responses against SARS-CoV-2 infections in humans.

Clinical presentations and outcomes of children with cancer and COVID-19: A systematic review.

Information regarding the novel coronavirus disease (COVID-19) in pediatric oncology is limited. We conducted a systematic review of the available published literature on children with cancer affected by COVID-19. The last date of the study search was October 20, 2020, and 33 studies comprising 226 children were included for the final analysis. Data were extracted in a predefined data collection form, and the variables were extracted and analyzed. Patients with hematological malignancies were more in number. Males and children on intensive treatment were more frequently affected. Fever was the commonest symptom. The disease was asymptomatic/mild in 48% and severe in 9.6%. Consolidation, peribronchial cuffing, and consolidation with ground glass opacities were the common imaging findings. Hydroxychloroquine was the most frequently used drug for COVID-19. About 10% of children required intensive care, and about 32% had oxygen requirements. The percentage of children who died due to COVID-19 was 4.9%. The severity, morbidity, and mortality of COVID-19 in pediatric oncology were more compared to the general pediatric population. This information can help in risk stratification for the management of COVID-19.

In silico drug designing for COVID-19: an approach of high-throughput virtual screening, molecular, and essential dynamics simulations.

Severe acute respiratory syndrome-coronavirus2 (SARS-CoV2), a new coronavirus has emerged in Wuhan city of China, December 2019 causing pneumonia named Coronavirus disease-19 (COVID-19), which has spread to the entire world. By January 2021, number of confirmed cumulative cases crossed ∼104 million worldwide. Till date, no effective treatment or drug is available for this virus. Availability of X-ray structures of SARS-CoV2 main protease (Mpro) provides the potential opportunity for structure-based drug designing. Here, we have made an attempt to do computational drug design by targeting main protease of SARS-CoV2. High-throughput virtual screening of million molecules and natural compounds databases were performed followed by docking. After that, the protein-ligand complexes were optimized and rescoring of binding energies were accomplished through molecular dynamics simulation and Molecular mechanics Poisson Boltzmann surface area approaches, respectively. In addition, conformational effect of various ligands on protein was also examined through essential dynamics simulation. Three compounds namely ZINC14732869, ZINC19774413, and ZINC19774479 were finally filtered that displayed better binding affinities than N3 (known) inhibitor and formed conformationally stable complexes. Hence, the current study features the potential novel inhibitors against main protease of SARS-CoV2 which might provide an effective therapeutic strategy against COVID-19.Communicated by Ramaswamy H. Sarma.

Mutant strains of SARS-CoV-2 are more prone to infect obese patient: a review.

The current review critically analyzes obesity as an important risk factor for increased predisposition towards coronavirus disease 2019 (COVID-19), its severity and causal death in current pandemic. Countries with higher prevalence of exposed obese individuals experienced the highest number of mortalities. The analysis also proved that individuals having more adipose tissue in body have a higher level of angiotensin-converting enzyme 2 (ACE2), which is identified as functional receptor for COVID-19. Therefore, obese individuals are worse in condition because of a higher presence of adiposity increases the number of ACE2 expressing cells. Furthermore, in silico interactions of ACE2 and different variants of coronavirus 2 (CoV-2) spike S1 protein suggest that mutant strains are more infectious than wildtype as they bind to host ACE2 protein with high binding affinities. Certain specific cancers including cervical cancer, pancreatic and rectal adenocarcinomas have more expression of such receptors and pose additional risk to already immunocompromised cancer patients. This review emphasizes obesity, as the covert risk factor of COVID-19 infection and sensitizes about of calorie restrictions, immunity building and preventive measures.

A systematic review of clinical and laboratory parameters of 3,000 COVID-19 cases.

The coronavirus disease 2019 (COVID-19) has spread worldwide. It is still a pandemic and poses major health problem across the globe. In our review, clinical characteristics and laboratory parameters of COVID-19 patients were compiled systematically, with special reference to pregnant women in order to understand the disease course. An extensive literature search on various scientific databases for relevant manuscripts was conducted, which yielded 7 manuscripts for final analysis. The most common symptoms were fever (85%), cough (70.63%), chest tightness (37.36%), expectoration (33.27%), fatigue (32%), dyspnea (31.95%), and shortness of breath (31.19%), while hemoptysis (1.0%) was the least common. The associated comorbidities were hypertension (21.6%) and diabetes (10.0%). In terms of hematological parameters, lower total leukocyte counts were observed in 65% of cases and biochemical parameters, patients demonstrated elevated levels of albumin (53.72%), lactate dehydrogenase (45.71%), and natriuretic peptide (34.84%); however, total bilirubin was elevated in only 8% of cases. In the acute inflammatory cytokine profile, C-reactive protein (59.0%), tumor necrosis factor (58.0%), erythrocyte sedimentation rate (57.0%), interleukin-2 (IL- 2, 54.0%), and IL-6 (52.0%) levels were increased, while prolactin levels (6.5%) were minimally elevated. The recovery rate was approximately 41%, and mortality was about 6.5%. The study also concluded that the clinical symptoms of COVID-19 were similar among pregnant and non-pregnant women. There was no evidence of vertical transmission of COVID-19 infection. This review critically analyzed COVID-19 as a public health hazard in order to help policy makers, health care givers, and primary physicians to promote early diagnosis and prevention.