Novel Antiviral Therapeutic Against SARS-CoV-2 and its Variants: Recent Developments and Future Perspectives (preprint)

Since the onset of coronavirus disease 2019 (COVID-19) pandemic, the virus kept developing and mutating into different variants over time that also gained increased transmissibility and spread in populations at a higher pace, culminating in successive waves of COVID-19 cases. The scientific community has developed vaccines and antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Realizing that growing SARS-CoV-2 variations significantly impact the efficacy of antiviral therapies and vaccines, we have summarized the appearance and attributes of SARS-CoV-2 variants for future perspectives in drug design, bringing up-to-date hints for developing therapeutic agents targeting the variants. The Omicron variant is among the most mutated form; its strong transmissibility and immune resistance capacity have prompted international worry. Most mutation sites currently being studied are located in the BCOV_S1_CTD of the S protein. Despite this, several hurdles remain, such as developing vaccination and pharmacological treatment efficacies for emerging mutants of SARS-CoV-2 strains. In this review, we present an updated viewpoint on the current issues faced by the emergence of various SARS-CoV-2 variants. Furthermore, we discuss the clinical studies conducted to assist the development and dissemination of vaccines, small molecule therapeutics, and therapeutic antibodies having broad-spectrum action against SARS-CoV-2 strains.

Virtual Mentoring: A Guide to Navigating a New Age in Mentorship.

Mentorship is a fundamental part of professional and personal growth. Over time, the fabric of mentorship has been transforming from typical one-on-one mentor-mentee relationship to other types including peer, group, speed, and virtual mentoring. When the COVID-19 pandemic hit, it caused major disruptions in many facets of life and career, including mentoring. In response to the COVID-19 pandemic, live meetings were canceled, and social distancing measures were enacted at many institutions. Thus, the traditional set-up, with a face-to-face mentor and mentee interaction, was impossible. Many virtual platforms were utilized to navigate through these restrictions. In this review, we highlight challenges in mentorship during the COVID-19 pandemic and how we implemented different strategies to promote mentorship.

Changes in Alcohol Consumption by Beverage Type Attributable to the COVID-19 Pandemic for 10 States, March 2020 to November 2020: An Ecological Simulation-based Analysis.

OBJECTIVES: Consumption of high potency alcohol is associated with greater healthcare burden, yet little attention has been placed on the change in types of alcohol consumed during the COVID-19 pandemic. We estimate the change in alcohol consumption by beverage type attributable to the COVID-19 pandemic. METHODS: The National Institute on Alcohol Abuse and Alcoholism provided apparent alcohol consumption ("consumption") by beverage type for 10 states for January 2017 through November 2020 based on sales and tax data. The 38-month period to February 2020 was used to train quasi-Poisson regression models. The models then predicted the monthly consumption based on the historical trends in the absence of the COVID-19 pandemic from March through November 2020. The difference between the observed and predicted is the change in consumption attributable to the COVID-19 pandemic. RESULTS: Beyond what was expected based on historical trends, spirits consumption increased significantly for 6 states (Colorado, Massachusetts, Missouri, North Dakota, Minnesota, and Tennessee) ranging from 4% (95% confidence interval [CI] 1%-6%) to 17% (95% CI 6%-28%) which is equivalent to 7 (95% CI 2-18) to 32 95% CI 12-48) excess standard spirits drinks per-capita; Alaska, Florida, Illinois, and Kentucky had no significant change. Wine consumption increased 10% (95% CI 3%-18%) in Colorado and 8% (95% CI 3%-12%) in Tennessee. Wine consumption in Alaska decreased 6% (95% CI, 3%-10%) and beer consumption decreased 8% (95% CI 4%-11%). CONCLUSIONS: During the COVID-19 pandemic, spirits consumption increased relative to wine and beer. Increased consumption of higher potency alcohol beverages could lead to higher alcohol-related healthcare and societal burden.

Management of Somatization in COVID-19: A Narrative Review.

Somatization refers to the condition in which psychological distress is shown in the form of somatic symptoms such as persistent headache, nausea, gastrointestinal discomfort, etc. Various predisposing factors, including familial such as high expressed emotion, poor parental care, genetic, biological, and demographic which includes age and gender, cognitive such as learning disabilities, psychiatric such as depression, anxiety, post-traumatic stress disorder, social, etc., play an essential role in saturation of the disease. During the time of the COVID-19 pandemic, psychological distress increased in the patients infected with the coronavirus due to some the factors such as social distancing from loved ones, lack of physical exercise, loss of income, loneliness due to quarantine, etc. Therefore, management and treatment of the disorder became essential, especially in coronavirus-infected patients, as it may lead to an increase in complications of the disease. Many studies have been conducted to identify the proper way to manage the condition. Treatments include pharmacological therapy and psychosocial interventions. Pharmacological therapy includes using various antidepressants, hypnotics, and sedatives such as benzodiazepines. For the treatment, mirtazapine is a secure and reliable antidepressant. Another drug, trizolobenzodiazepine adinazolam, was also very useful in treating patients. In some randomized experiments, alprazolam significantly outperformed amitryptiline in reducing the symptoms. Psychosocial interventions include sessions such as cognitive behavioral therapy (CBT), mindfulness-based cognitive therapy, relaxation training, meditation, and psychological interventions such as enhancing multidimensional social help, modifying cognitive assessment, directing positive coping, and inspiring positive emotions.

In‐silico Computational Investigations of AntiViral Lignan Derivatives as Potent Inhibitors of SARS CoV‐2

Due to alarming outbreak of pandemic COVID‐19 in recent times, there is a strong need to discover and identify new antiviral agents acting against SARS CoV‐2. Among natural products, lignan derivatives have been found effective against several viral strains including SARS CoV‐2. Total of twenty‐seven reported antiviral lignan derivatives of plant origin have been selected for computational studies to identify the potent inhibitors of SARS CoV‐2. Molecular docking study has been carried out in order to predict and describe molecular interaction between active site of enzyme and lignan derivatives. Out of identified hits, clemastatin B and erythro‐strebluslignanol G demonstrated stronger binding and high affinity with all selected proteins. Molecular dynamics simulation studies of clemastin B and savinin against promising targets of SARS CoV‐2 have revealed their inhibitory potential against SARS CoV‐2. In fine, in‐silico computational studies have provided initial breakthrough in design and discovery of potential SARS CoV‐2 inhibitors. The present work involve the in‐silico discovery of liganan derivatives as SARS CoV‐2 inhibitors against more than one promising antiviral targets invovling the study of ligand binding strength through molecular docking, assessment of drug likeliness using Lipinski's filters and MD simulations‐based assessment of the stability of the ligands within active sites of antiviral targets.

Exploration of Novel Lichen Compounds as Inhibitors of SARS-CoV-2 Mpro: Ligand-Based Design, Molecular Dynamics, and ADMET Analyses.

In the year 2019-2020, the whole world witnessed the spread of a disease called COVID-19 caused by SARS-CoV-2. A number of effective drugs and vaccine has been formulated to combat this outbreak. For the development of anti-COVID-19 drugs, the main protease (Mpro) is considered a key target as it has rare mutations and plays a crucial role in the replication of the SARS CoV-2. In this study, a library of selected lichen compounds was prepared and used for virtual screening against SARS-CoV-2 Mpro using molecular docking, and several hits as potential inhibitors were identified. Remdesivir was used as a standard inhibitor of Mpro for its comparison with the identified hits. Twenty-six compounds were identified as potential hits against Mpro, and these were subjected to in silico ADMET property prediction, and the compounds having favorable properties were selected for further analysis. After manual inspection of their interaction with the binding pocket of Mpro and binding affinity score, four compounds, namely, variolaric acid, cryptostictinolide, gyrophoric acid, and usnic acid, were selected for molecular dynamics study to evaluate the stability of complex. The molecular dynamics results indicated that except cryptostictinolide, all the three compounds made a stable complex with Mpro throughout a 100-ns simulation time period. Among all, usnic acid seems to be more stable and effective against SARS-CoV-2 Mpro. In summary, our findings suggest that usnic acid, variolaric acid, and gyrophoric acid have potential to inhibit SARS-Cov-2 Mpro and act as a lead compounds for the development of antiviral drug candidates against SARS-CoV-2.

Mental health problems in health-care workers working in COVID-19 quarantine centers

Background: The coronavirus disease-19 (COVID-19) pandemic in India has put health-care workers (HCWs) under intense pressure and has led to immense psychological stress due to factors including a high risk of infection, inadequate protection from contamination, overwork, cutting-off with families, and exhaustion. The unprecedented stressful conditions are causing mental health problems such as stress, anxiety, depression, disturbed sleep, irritability, fear, and panic. The present study was carried out to investigate the mental health problems among HCWs working in close proximity with COVID-19 patients in quarantine centers and to explore the relevant influencing factors for the development of psychological interventions for them. Subject and Methods: HCWs working in COVID-19 quarantine centers in Ajmer were interviewed for exploring mental health problems in a cross-sectional study carried out at JLN Medical College, Ajmer, India. Depressive symptoms, anxiety, and stress among HCWs were assessed using the Depression Anxiety Stress Scale and Perceived Stress Scale (PSS). Relevant data were analyzed, and comparisons between different groups were performed using the two independent sample t-tests. All statistical analyses were performed using the SPSS software version 22.0 for Windows. Results: 53.57% (n = 30) of participants were suffering from depressive symptoms, 64.28% (n = 36) were suffering from anxiety symptoms, and 78.6% (n = 47) were suffering from stress. HCWs living in joint families were more affected by depression (P = 0.02). Both anxiety and stress were more commonly reported by HCWs of age <30, females, nurses and those living in joint families, but difference was statistically insignificant. Conclusion: The present study demonstrated that a considerable number of HCWs were suffering from mental health problems such as depression, anxiety, and stress. It is important to have periodic mental health assessment of HCWs dealing with COVID-19 patients.

COVID-19: A review of its clinical features, effects on gastrointestinal system and possibility of faecal transmission

In China, Wuhan in the province of China, COVID-19 a patient suffering from pneumonia was tested and to identify the cause, the throat swab of the patient was tested. On 7th January 2020 WHO declared the identification as COVID-19. And then it was proclaimed as a pandemic. It classically causes a respiratory illness presenting as a mild cough, fever and dyspnoea. However, sev-eral investigators have advocated the involvement of the gastrointestinal tract and liver in COVID-19 infection similar to other coronavirus infections. Further research studies have shown results that are expanding the possibility of faecal transmission because RT-PCR assessment has shown significant evidence for the presence of virus not only in oropharyngeal samples but also in stool samples. Studies have shown that virus in stool samples have got positive results even after the illness has resolved, and two respiratory tests were done 24 hours after COVID-19 being tested negative. The review article summarises the different findings of the clinical presentation of COVID-19. It sheds light on the effects of COVID-19 in the gastrointestinal system along with the reasons for the high possibility of transmission of COVID-19 through the faecal-oral route.

Positive aspects of covid 19 pandemic: A blessing in disguise

COVID 19 is undeniably one of the deadliest diseases that humanity has ever seen. It continues to affect the lives and livelihood of people appallingly across the world. Maximum discussions focus towards the apprehension of catching the infection, dwelling in homes, overpopulated nursing homes and shut down of all kinds. But, here let’s discuss the positive side of COVID 19 pandemic.As COVID 19 has spread its influence all over the world, affected countries have either announced lockdown or have implemented severe restrictions in their respective countries. Because of this, everyone dwells in their homes. Thus, exercising social distancing and functioning from home. All of the above is directed at restricting the transmission of coronavirus and expectantly ostracising the fatality from COVID 19. These transformations have also brought about some unanticipated emanations;some good things have come out of the pandemic as well. Positive effects of COVID 19 are seen on reduced road traffic, and road traffic accidents lowered levels of air pollution which has to lead to lowered heart attack rates and rejuvenating environment. Crime rates have fallen, and expenses are reduced in most places. Community action, communication amongst families, behaviour, sanitation, hygiene, online and distance education has positively impacted by COVID 19 pandemic. COVID 19 despite a bane for humans, can be thought of a boon for living beings. The habitats and elements have been purified with the stringent use of petrochemical products. To breathe fresh air and to consume purified water is a boon by itself. Now, it is time for humans to lead a caring life to every bounty bestowed on them by Nature. This thoughtful and considerate life will give hope for a healthy, stress-free life.