Antibodies to Commonly Circulating Viral Pathogens Modulate Serological Response to Severe Acute Respiratory Syndrome Coronavirus 2 Infection

The purpose of this study was to determine the seropositivity of circulating viral pathogens and their association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity. In a cross-sectional design, inhabitants (aged 10-60 years) of the slum and surrounding non-slum areas of Dhaka and Chattogram Metropolitan cities in Bangladesh were enrolled from October 2020 to February 2021. Antibodies to SARS-CoV-2, influenza B, parainfluenza, respiratory syncytial virus (RSV), human coronavirus HKU1 (HCoV-HKU1), dengue and chikungunya viruses were determined in plasma. The association of SARS-CoV-2 seropositivity with seropositivity to other viruses was assessed using the multi-variate logistic regression model. Seroprevalence of SARS-CoV-2, influenza B, RSV, dengue, chikungunya, HCoV-HKU1 and the parainfluenza virus were 68.3%, 98%, 50.0%, 16.5%, 15.5%, 3.36% and 0.0%, respectively. Individuals seropositive for RSV had lower odds (OR = 0.60;95% CI= 0.49, 0.73) of SARS-CoV-2 seropositivity compared to RSV-seronegative individuals. Conversely, higher odds of SARS-CoV-2 seropositivity were observed in participants seropositive for dengue (OR= 1.73;95% CI = 1.14, 2.66, only in slum) or chikungunya (OR = 1.48;95% CI = 1.11, 1.95) compared to their seronegative counterparts. The study findings indicated that exposure to vector-borne virus dengue or chikungunya enhance, while antibodies to respiratory virus RSV decrease, the serological response to SARS-CoV-2.

Roles of the polybasic furin cleavage site of spike protein in SARS-CoV-2 replication, pathogenesis, and host immune responses and vaccination.

The polybasic furin cleavage site insertion with four amino acid motifs (PRRA) in spike protein's S1/S2 junction site is important in determining viral infectivity, transmission, and host range. However, there is no review so far explaining the effect of the furin cleavage site of the spike protein on SARS-CoV-2 replication and pathogenesis in the host and immune responses and vaccination. Therefore, here we specifically focused on genomic evolution and properties of the cleavage site of spike protein in the context of SARS-CoV-2 followed by its effect on viral entry, replication, and pathogenesis. We also explored whether the spike protein furin cleavage site affected the host immune responses and SARS-CoV-2 vaccination. This review will help to provide novel insights into the effects of polybasic furin cleavage site on the current COVID-19 pandemic.

Active site-specific quantum tunneling of hACE2 receptor to assess its complexing poses with selective bioactive compounds in co-suppressing SARS-CoV-2 influx and subsequent cardiac injury.

OBJECTIVE: This research aims to study the target specificity of selective bioactive compounds in complexing with the human angiotensin-converting enzyme (hACE2) receptor to impede the severe acute respiratory syndrome coronavirus 2 influx mechanism resulting in cardiac injury and depending on the receptor's active site properties and quantum tunneling. MATERIALS AND METHODS: A library of 120 phytochemical ligands was prepared, from which 5 were selected considering their absorption, distribution, metabolism, and excretion (ADMET) and quantitative structure-activity relationship (QSAR) profiles. The protein active sites and belonging quantum tunnels were defined to conduct supramolecular docking of the aforementioned ligands. The hydrogen bond formation and hydrophobic interactions between the ligand-receptor complexes were studied following the molecular docking steps. A comprehensive molecular dynamic simulation (MDS) was conducted for each of the ligand-receptor complexes to figure out the values - root mean square deviation (RMSD) (Å), root mean square fluctuation (RMSF) (Å), H-bonds, Cα, solvent accessible surface area (SASA) (Å2), molecular surface area (MolSA) (Å2), Rg (nm), and polar surface area (PSA) (Å). Finally, computational programming and algorithms were used to interpret the dynamic simulation outputs into their graphical quantitative forms. RESULTS: ADMET and QSAR profiles revealed that the most active candidates from the library to be used were apigenin, isovitexin, piperolactam A, and quercetin as test ligands, whereas serpentine as the control. Based on the binding affinities of supramolecular docking and the parameters of molecular dynamic simulation, the strength of the test ligands can be classified as isovitexin > quercetin > piperolactam A > apigenin when complexed with the hACE2 receptor. Surprisingly, serpentine showed lower affinity (-8.6 kcal/mol) than that of isovitexin (-9.9 kcal/mol) and quercetin (-8.9 kcal/mol). The MDS analysis revealed all ligands except isovitexin having a value lower than 2.5 Ǻ. All the test ligands exhibited acceptable fluctuation ranges of RMSD (Å), RMSF (Å), H-bonds, Cα, SASA (Å2), MolSA (Å2), Rg (nm), and PSA (Å) values. CONCLUSION: Considering each of the parameters of molecular optimization, docking, and dynamic simulation interventions, all of the test ligands can be suggested as potential targeted drugs in blocking the hACE2 receptor.

Emerging Role of Neuropilin-1 and Angiotensin-Converting Enzyme-2 in Renal Carcinoma-Associated COVID-19 Pathogenesis.

Neuropilin-1 (NRP1) is a recently identified glycoprotein that is an important host factor for SARS-CoV-2 infection. On the other hand, angiotensin-converting enzyme-2 (ACE2) acts as a receptor for SARS-CoV-2. Additionally, both NRP1 and ACE2 express in the kidney and are associated with various renal diseases, including renal carcinoma. Therefore, the expression profiles of NRP1 and ACE2 in kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) patients from the various cancer databases were investigated along with their impact on patients' survivability. In addition, coexpression analysis of genes involved in COVID-19, KIRC, and KIRP concerning NRP1 and ACE2 was performed. The results demonstrated that both t NRP1 and ACE2 expressions are upregulated in KIRC and KIRP compared to healthy conditions and are significantly correlated with the survivability rate of KIRC patients. A total of 128 COVID-19-associated genes are coexpressed, which are positively associated with NRP1 and ACE2 both in KIRC and KIRP. Therefore, it might be suggested that, along with the ACE2, high expression of the newly identified host factor NRP1 in renal carcinomas may play a vital role in the increased risk of SARS-CoV-2 infection and survivability of COVID-19 patients suffering from kidney cancers. The findings of this investigation will be helpful for further molecular studies and prevention and/or treatment strategies for COVID-19 patients associated with renal carcinomas.

SARS-CoV-2 host diversity: An update of natural infections and experimental evidence.

Coronavirus disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is now a pandemic threat. This virus is supposed to be spread by human to human transmission. Cellular angiotensin-converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2 which is identical or similar in different species of animals such as pigs, ferrets, cats, orangutans, monkeys, and humans. Moreover, a recent study predicted that dogs might be secondary hosts during the evolution of SARS-CoV-2 from bat to human. Therefore, there is a possibility of spreading SARS-CoV-2 through domestic pets. There are now many reports of SARS-CoV-2 positive cases in dogs, cats, tigers, lion, and minks. Experimental data showed ferrets and cats are highly susceptible to SARS-CoV-2 as infected by virus inoculation and can transmit the virus directly or indirectly by droplets or airborne routes. Based on these natural infection reports and experimental data, whether the pets are responsible for SARS-CoV-2 spread to humans; needs to be deeply investigated. Humans showing clinical symptoms of respiratory infections have been undergoing for the COVID-19 diagnostic test but many infected people and few pets confirmed with SARS-CoV-2 remained asymptomatic. In this review, we summarize the natural cases of SARS-CoV-2 in animals with the latest researches conducted in this field. This review will be helpful to think insights of SARS-CoV-2 transmissions, spread, and demand for seroprevalence studies, especially in companion animals.