Evaluation of SARS-CoV-2 Main Protease Inhibitors Using a Novel Cell-Based Assay.

As an essential enzyme of SARS-CoV-2, main protease (MPro) triggers acute toxicity to its human cell host, an effect that can be alleviated by an MPro inhibitor. Using this toxicity alleviation, we developed an effective method that allows a bulk analysis of the cellular potency of MPro inhibitors. This novel assay is advantageous over an antiviral assay in providing precise cellular MPro inhibition information to assess an MPro inhibitor. We used this assay to analyze 30 known MPro inhibitors. Contrary to their strong antiviral effects and up to 10 µM, 11a, calpain inhibitor II, calpain XII, ebselen, bepridil, chloroquine, and hydroxychloroquine showed relatively weak to undetectable cellular MPro inhibition potency implicating their roles in interfering with key steps other than just the MPro catalysis in the SARS-CoV-2 life cycle. Our results also revealed that MPI5, MPI6, MPI7, and MPI8 have high cellular and antiviral potency. As the one with the highest cellular and antiviral potency among all tested compounds, MPI8 has a remarkable cellular MPro inhibition IC50 value of 31 nM that matches closely to its strong antiviral effect with an EC50 value of 30 nM. Therefore, we cautiously suggest exploring MPI8 further for COVID-19 preclinical tests.

Evaluation of SARS-CoV-2 Main Protease Inhibitors Using a Novel Cell-Based Assay

As an essential enzyme of SARS-CoV-2, main protease (MPro) triggers acute toxicity to its human cell host, an effect that can be alleviated by an MPro inhibitor. Using this toxicity alleviation, we developed an effective method that allows a bulk analysis of the cellular potency of MPro inhibitors. This novel assay is advantageous over an antiviral assay in providing precise cellular MPro inhibition information to assess an MPro inhibitor. We used this assay to analyze 30 known MPro inhibitors. Contrary to their strong antiviral effects and up to 10 μM, 11a, calpain inhibitor II, calpain XII, ebselen, bepridil, chloroquine, and hydroxychloroquine showed relatively weak to undetectable cellular MPro inhibition potency implicating their roles in interfering with key steps other than just the MPro catalysis in the SARS-CoV-2 life cycle. Our results also revealed that MPI5, MPI6, MPI7, and MPI8 have high cellular and antiviral potency. As the one with the highest cellular and antiviral potency among all tested compounds, MPI8 has a remarkable cellular MPro inhibition IC50 value of 31 nM that matches closely to its strong antiviral effect with an EC50 value of 30 nM. Therefore, we cautiously suggest exploring MPI8 further for COVID-19 preclinical tests. A cell sorting-based assay was developed to study about 30 SARS-CoV-2 main protease inhibitors, revealing MPI8 as the most potent one and others with likely different mechanisms.

Case Report: Paucisymptomatic College-Age Population as a Reservoir for Potentially Neutralization-Resistant Severe Acute Respiratory Syndrome Coronavirus 2 Variants.

To better understand the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant lineage distribution in a college campus population, we carried out viral genome surveillance over a 7-week period from January to March 2021. Among the sequences were three novel viral variants: BV-1 with a B.1.1.7/20I genetic background and an additional spike mutation Q493R, associated with a mild but longer-than-usual COVID-19 case in a college-age person, BV-2 with a T478K mutation on a 20B genetic background, and BV-3, an apparent recombinant lineage. This work highlights the potential of an undervaccinated younger population as a reservoir for the spread and generation of novel variants. This also demonstrates the value of whole genome sequencing as a routine disease surveillance tool.

Sleep Quality and Physical Activity as Predictors of Mental Wellbeing Variance in Older Adults during COVID-19 Lockdown: ECLB COVID-19 International Online Survey

BACKGROUND: The COVID-19 lockdown could engender disruption to lifestyle behaviors, thus impairing mental wellbeing in the general population. This study investigated whether sociodemographic variables, changes in physical activity, and sleep quality from pre- to during lockdown were predictors of change in mental wellbeing in quarantined older adults. METHODS: A 12-week international online survey was launched in 14 languages on 6 April 2020. Forty-one research institutions from Europe, Western-Asia, North-Africa, and the Americas, promoted the survey. The survey was presented in a differential format with questions related to responses "pre" and "during" the lockdown period. Participants responded to the Short Warwick-Edinburgh Mental Wellbeing Scale, the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and the short form of the International Physical Activity Questionnaire. RESULTS: Replies from older adults (aged >55 years, n = 517), mainly from Europe (50.1%), Western-Asia (6.8%), America (30%), and North-Africa (9.3%) were analyzed. The COVID-19 lockdown led to significantly decreased mental wellbeing, sleep quality, and total physical activity energy expenditure levels (all p < 0.001). Regression analysis showed that the change in total PSQI score and total physical activity energy expenditure (F_{(2, 514)} = 66.41 p < 0.001) were significant predictors of the decrease in mental wellbeing from pre- to during lockdown (p < 0.001, R²: 0.20). CONCLUSION: COVID-19 lockdown deleteriously affected physical activity and sleep patterns. Furthermore, change in the total PSQI score and total physical activity energy expenditure were significant predictors for the decrease in mental wellbeing.

Immuno-informatics approach based epitopes prediction for vaccine design against severe acute respiratory syndrome coronavirus-2

Severe Acute Respiratory Syndrome Coronavirus-2 (COVID-19) outbreak worldwide which is rapidly spreading through human transmission is increasing the mortality rates. It is a serious concern for the clinicians to treat the infected from respiratory complications. But, there are no suitable medicines available for immediate therapy. Hence, development of vaccines for the COVID-19 is the primary focus of the researchers. Immuno-informatics based approach for identifying the highly immunogenic B and T-cell epitopes of the surface glycoprotein of the SARS-CoV-2 was performed in IEDB server. The chosen epitopes were analysed for the binding potential with the MHC alleles using Patch dock server. The results revealed greater binding interactions between the selected peptides and MHC-Dd allele (co-crystallised with TAPBPR). Recognized epitopes may serve as target candidates for development of vaccines to combat the dreadful communicable infectious disease. © 2020, Advanced Scientific Research. All rights reserved.

Potential anti-covid-19 drug options

COVID-19, the infection caused by the recently identified coronavirus, is currently a disease with no pharmaceutical weapons against it. Researchers across the world are racing to find the investigation of existing drugs for new therapeutic purposes (Drug repositioning, also called drug repurposing) to develop safe and effective COVID-19 treatments. Other research directions include the development of a COVID-19 vaccine. Developing new vaccines takes time, and they must be rigorously tested and confirmed safe via clinical trials before they can be routinely used in humans. WHO launched the multinational trial to jumpstart the search for coronavirus drugs. The drugs to be tested are the antiviral drug remdesivir;a combination of two HIV drugs, lopinavir and ritonavir, lopinavir, and ritonavir plus interferon beta and the antimalarial drug chloroquine and Hydroxy Chloroquine. All show some evidence of effectiveness against the SARS-CoV 2 virus, which causes COVID-19, either in vitro and animal studies. The four drugs or combinations will be compared to what is called a standard of care the regular support hospitals treating these patients use at present, such as supplementary oxygen when desired. Clinical trials in China and several other countries have been conducting on drugs such as Remdesivir, Lopinavir + Ritonavir, Tenofovir, Oseltamivir, Baloxivir marboxil, Umifenovir, Novaferon, IFNs, Chloroquine, Traditional Chinese Medicines: Lianhua Qingwen.