In silico phytochemical repurposing of natural molecules as entry inhibitors against RBD of the spike protein of SARS-CoV-2 using molecular docking studies

The receptor binding domain (RBD) of Spike-protein (S-protein) is responsible for virus entry via interaction with host protein ACE2 (angiotensin-converting enzyme 2), present on the cell surface of humans. Therefore, S-protein is an important target to block the entry of the SARS-CoV-2 into the cell for further growth. In the present study, phytochemical repurposing of natural molecules: narirutin, naringin, neohesperidin and hesperidin were performed against the RBD S-protein/ACE2 interface as well as the RBD of the S-protein using molecular docking. These natural molecules were found to have structural similarity to each other and had binding potential against the viral infections. It is first time reported here that the naringin and narirutin are having binding potential against both RBD S-protein/ACE2 interface and active site of RBD of S-protein using binding mode analysis. Hence, this study will open avenues for multitargeting similar natural molecules binding against the SARS-CoV-2 proteins as all reports are made in this single study.

Plant Extracts and Phytochemicals, a Promising Strategy Against Oral Lichen Planus: a review on Clinical Trials.

BACKGROUND: Oral lichen planus (OLP) is an autoimmune disease that distress keratinized cells of the oral epithelium. Topical corticosteroids and other potential therapies like immunosuppressives, hydroxychloroquine, azathioprine, mycophenolate, dapsone, retinoids, biologic agents are used for the management of OLP. However, their effectiveness, best dose, duration of treatment and safety remain mostly unidentified. Moreover, recurrence of disease and dose-related side effects are the other issues. OBJECTIVE: The primary objective of the review is to explore the existing clinical trials for the efficacy of phytochemicals in treating OLP in comparison to corticosteroids. A comprehensive information about their mode of action is also discussed. METHOD: We have discussed different clinical trials conducted on various phytochemicals and plant extracts/formulations like curcumin, lycopene, quercetin, glycyrrhizin, purslane, raspberry, aloe vera gel and aloe vera mouthwash for the treatment of OLP. RESULT: The current therapy for the management of OLP has numerous adverse effects and requires a long-term treatment. Phytochemicals can be a very good alternative in overcoming these side effects and reducing the course of treatment. CONCLUSION: Herbal extracts and their formulations can be an effective alternative to the current therapy due to their proven therapeutic effects, reduced side effects, long-term applicability, prevention of recurrence as well as progression into cancer.

Inter-laboratory testing as a strategy for external quality assessment for qualitative detection of SARS-CoV-2 by real-time RT-PCR testing in India.

To implement the strategy of test, track and treat to tackle the ongoing COVID-19 pandemic, the number of real-time RT-PCR-based testing laboratories was increased for diagnosis of SARS-CoV-2 in the country. To ensure reliability of the laboratory results, the Indian Council of Medical Research initiated external quality assessment (EQA) by deploying inter-laboratory quality control (ILQC) activity for these laboratories by nominating 34 quality control (QC) laboratories. This report presents the results of this activity for a period of September 2020 till November 2020. A total of 597 laboratories participated in this activity and 86 per cent of these scored ≥90 per cent concordance with QC laboratories. This ILQC activity showcased India's preparedness in quality diagnosis of SARS-CoV-2.

A two-step process for in silico screening to assess the performance of qRTPCR kits against variant strains of SARS-CoV-2.

BACKGROUND: Since inception of the COVID-19 pandemic, early detection and isolation of positive cases is one of the key strategies to restrict disease transmission. Real time reverse transcription polymerase chain reaction (qRTPCR) has been the mainstay of diagnosis. Most of the qRTPCR kits were designed against the target genes of original strain of SARS-CoV-2. However, with the emergence of variant strains of SARS-CoV-2, sensitivity of the qRTPCR assays has reportedly reduced. In view of this, it is critical to continuously monitor the performance of the qRTPCR kits in the backdrop of variant strains of SARS-CoV-2. Real world monitoring of assay performance is challenging. Therefore, we developed a two-step in-silico screening process for evaluating the performance of various qRTPCR kits used in India. RESULTS: We analysed 73 qRT-PCR kits marketed in India, against the two SARS-CoV-2 VoCs. Sequences of both Delta (B.1.617.2) and Omicron (B.1.1.529) VoCs submitted to GISAID within a specific timeframe were downloaded, clustered to identify unique sequences and aligned with primer and probe sequences. Results were analysed following a two-step screening process. Out of 73 kits analysed, seven were unsatisfactory for detection of both Delta and Omicron VoCs, 10 were unsatisfactory for Delta VoC whereas 2 were unsatisfactory for only Omicron VoC. CONCLUSION: Overall, we have developed a useful screening process for evaluating the performance of qRTPCR assays against Delta and Omicron VoCs of SARS-CoV-2 which can be used for detecting SARS-CoV-2 VoCs that may emerge in future and can also be redeployed for other evolving pathogens of public health importance.

Preclinical immunogenicity and efficacy of a candidate COVID-19 vaccine based on a vesicular stomatitis virus-SARS-CoV-2 chimera.

BACKGROUND: To investigate a vaccine technology with potential to protect against coronavirus disease 2019 (COVID-19) and reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a single vaccine dose, we developed a SARS-CoV-2 candidate vaccine using the live vesicular stomatitis virus (VSV) chimeric virus approach previously used to develop a licensed Ebola virus vaccine. METHODS: We generated a replication-competent chimeric VSV-SARS-CoV-2 vaccine candidate by replacing the VSV glycoprotein (G) gene with coding sequence for the SARS-CoV-2 Spike glycoprotein (S). Immunogenicity of the lead vaccine candidate (VSV∆G-SARS-CoV-2) was evaluated in cotton rats and golden Syrian hamsters, and protection from SARS-CoV-2 infection also was assessed in hamsters. FINDINGS: VSV∆G-SARS-CoV-2 delivered with a single intramuscular (IM) injection was immunogenic in cotton rats and hamsters and protected hamsters from weight loss following SARS-CoV-2 challenge. When mucosal vaccination was evaluated, cotton rats did not respond to the vaccine, whereas mucosal administration of VSV∆G-SARS-CoV-2 was found to be more immunogenic than IM injection in hamsters and induced immunity that significantly reduced SARS-CoV-2 challenge virus loads in both lung and nasal tissues. INTERPRETATION: VSV∆G-SARS-CoV-2 delivered by IM injection or mucosal administration was immunogenic in golden Syrian hamsters, and both vaccination methods effectively protected the lung from SARS-CoV-2 infection. Hamsters vaccinated by mucosal application of VSV∆G-SARS-CoV-2 also developed immunity that controlled SARS-CoV-2 replication in nasal tissue. FUNDING: The study was funded by Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA. Parts of this research was supported by the Biomedical Advanced Research and Development Authority (BARDA) and the Defense Threat Reduction Agency (DTRA) of the US Department of Defense.

Global respiratory virus surveillance: strengths, gaps, and way forward.

CURRENT SITUATION: The global influenza surveillance and response system (GISRS), coordinated by the World Health Organization (WHO), is a global framework for surveillance of influenza and other respiratory viruses, data collection, laboratory capacity building, genomic data submission and archival, standardization, and calibration of reagents and vaccine strains, production of seasonal influenza vaccines and creating a facilitatory regulatory environment for the same. GAPS: WHO-designated national influenza centers (NICs) are entrusted with establishing surveillance in their respective countries. National and subnational surveillance remains weak in most parts of the world because of varying capacities of the NICs, lack of funds, poor human and veterinary surveillance mechanisms, lack of intersectoral coordination, and varying commitments of the local government. WAY FORWARD: As influenza viruses have a wide variety of nonhuman hosts, it is critical to strengthen surveillance at local levels for timely detection of untypable or novel strains with potential to cause epidemics or pandemics. In this article, we have proposed possible strategies to strengthen and expand local capacities for respiratory virus surveillance through the designated NICs of the WHO.

External quality assessment of COVID-19 real time reverse transcription PCR laboratories in India.

Sudden emergence and rapid spread of COVID-19 created an inevitable need for expansion of the COVID-19 laboratory testing network across the world. The strategy to test-track-treat was advocated for quick detection and containment of the disease. Being the second most populous country in the world, India was challenged to make COVID-19 testing available and accessible in all parts of the country. The molecular laboratory testing network was augmented expeditiously, and number of laboratories was increased from one in January 2020 to 2951 till mid-September, 2021. This rapid expansion warranted the need to have inbuilt systems of quality control/ quality assurance. In addition to the ongoing inter-laboratory quality control (ILQC), India implemented an External Quality Assurance Program (EQAP) with assistance from World Health Organization (WHO) and Royal College of Pathologists, Australasia. Out of the 953 open system rRTPCR laboratories in both public and private sector who participated in the first round of EQAP, 891(93.4%) laboratories obtained a passing score of > = 80%. The satisfactory performance of Indian COVID-19 testing laboratories has boosted the confidence of the public and policy makers in the quality of testing. ILQC and EQAP need to continue to ensure adherence of the testing laboratories to the desired quality standards.

Clinico-Radiological-Pathological Correlation of Visual Loss in COVID-Associated Rhino-Orbito-Cerebral Mucormycosis.

PURPOSE: To correlate the clinical, radiological, and histopathological features in Covid-associated Rhino-orbito-cerebral mucormycosis cases presenting with acute visual loss. DESIGN: Cross-sectional study. METHODS: Covid-associated Rhino-orbito-cerebral mucormycosis cases with unilateral visual loss, planned for exenteration, underwent orbital and ophthalmological ocular examination. The available radiological sequences, doppler ultrasonography and histopathology findings were correlated with clinical manifestations. RESULTS: The median age was 51 years and the male: female ratio was 3:1. All except one presented with unilateral ophthalmoplegia. The ocular media were hazy in 2 eyes. In 8 eyes, retinal changes were suggestive of occlusion of CRA (6), combined occlusion of CRA and central retinal vein (1), and myopic degeneration with hypertensive retinopathy (1). The contralateral eye showed retinal ischemic changes in one patient. Radiological imaging showed orbital apex involvement in the 10 affected eyes and one contralateral eye. Ipsilateral cavernous sinus thrombosis, diffusion restriction on MRI of optic nerve, internal carotid artery narrowing/thrombosis, and cortical watershed infarcts were seen in 8, 4, 4, and 2 cases, respectively. The blood flow in CRA and ophthalmic artery was absent or reduced in all the 10 affected eyes and in 1 contralateral eye. On histopathology, orbital fat necrosis, fungal hyphae, acute inflammation, granuloma formation, ischemic thrombosis of ophthalmic artery was observed in 10 specimens. CRA was patent in 9 and thrombosed in 1 eye. Optic nerve was ischemic in 8 and viable in 2 eyes. CONCLUSION: Acute visual loss in ROCM cases is associated with orbital apex involvement and thrombotic ischemia of ophthalmic artery. Cessation of flow in CRA possibly occurs secondary to ophthalmic artery thrombosis.

Psychological, social and economic impact of COVID 19 on the working population of India: Exploratory factor analysis approach.

The purpose of this study is to unravel the effects of COVID-19 on the psychological, social, and economic well-being of the working population of India. To achieve the objectives of the study, an online survey was conducted, focusing on aspects like psycho-social well-being, safety, financial stability, and work from home implications. We have used exploratory factor analysis (EFA), t-test, and analysis of variance technique to find the underlying factors. The findings suggest that the female population of the society is more vulnerable to social-psychological and organizational stress. In terms of financial stability, private employees are more unstable as compared to government employees. Based on the standard of living, people of type 1 cities are more affected by the COVID-19 outbreak compared to the people of type 2 and type 3 cities. Hence, by and large, female employees, employees working in the private sector, and employees residing in type 1 cities are more likely to have the behavioral manifestation of negative psychological states caused by this pandemic. The findings will assist policymakers in understanding and devising appropriate policies considering the psycho-social and work-related economic issues faced by the working population of India during the COVID- 19 pandemic.

Clinical Characterization and Genomic Analysis of Samples from COVID-19 Breakthrough Infections during the Second Wave among the Various States of India.

From March to June 2021, India experienced a deadly second wave of COVID-19, with an increased number of post-vaccination breakthrough infections reported across the country. To understand the possible reason for these breakthroughs, we collected 677 clinical samples (throat swab/nasal swabs) of individuals from 17 states/Union Territories of the country who had received two doses (n = 592) and one dose (n = 85) of vaccines and tested positive for COVID-19. These cases were telephonically interviewed and clinical data were analyzed. A total of 511 SARS-CoV-2 genomes were recovered with genome coverage of higher than 98% from both groups. Analysis of both groups determined that 86.69% (n = 443) of them belonged to the Delta variant, along with Alpha, Kappa, Delta AY.1, and Delta AY.2. The Delta variant clustered into four distinct sub-lineages. Sub-lineage I had mutations in ORF1ab A1306S, P2046L, P2287S, V2930L, T3255I, T3446A, G5063S, P5401L, and A6319V, and in N G215C; Sub-lineage II had mutations in ORF1ab P309L, A3209V, V3718A, G5063S, P5401L, and ORF7a L116F; Sub-lineage III had mutations in ORF1ab A3209V, V3718A, T3750I, G5063S, and P5401L and in spike A222V; Sub-lineage IV had mutations in ORF1ab P309L, D2980N, and F3138S and spike K77T. This study indicates that majority of the breakthrough COVID-19 clinical cases were infected with the Delta variant, and only 9.8% cases required hospitalization, while fatality was observed in only 0.4% cases. This clearly suggests that the vaccination does provide reduction in hospital admission and mortality.

Assessing the Impact of COVID-19 Pandemic on the Stock and Commodity Markets Performance and Sustainability: A Comparative Analysis of South Asian Countries

COVID-19 is certainly the first sustainability crisis of the 21st century. The paper examines the impact of COVID-19 on the Indian stock and commodity markets during the different phases of lockdown. In addition, the effect of COVID-19 on the Indian stock and commodity markets during the first and second waves of the COVID-19 spread was compared. A comparative analysis of the stock market performances and sustainability of selected South Asian countries is also included in the study, which covers the lockdown period as well as the time frame of the first and second waves of COVID-19 spread. To examine the above relationship, the conventional Welch test, heteroskedastic independent t-test, and the GMM multivariate analysis is employed, on the stock return, gold prices, and oil prices. The findings conclude that during the different phases of lockdown in India, COVID-19 has a negative and significant impact on oil prices and stock market performance. However, in terms of gold prices, the effect is positive and significant. The results of the first wave of COVID-19 infection also corroborate with the above findings. However, the results are contradictory during the second wave of coronavirus infection. Furthermore, the study also substantiates that COVID-19 has significantly affected the stock market performances of selected South Asian countries. However, the impact on the stock market performances was only for a short period and it diminished in the second wave of COVID-19 spread in all the selected South Asian countries. The findings contribute to the research on the stock and commodity market impact of a pandemic by providing empirical evidence that COVID-19 has spill-over effects on stock markets and commodity market performances. This result also helps investors in assessing the trends of the stock and commodity markets during the pandemic outbreak.

Addressing the Challenges in dental practice during Covid-19: A review

Covid-19 was declared as global pandemic by WHO. World is not unknown to the family of coronaviruses due to previous epidemic caused by SARS and MERS. Healthcare professions have from time to time change their ways of practicing because of the direct threat posed by such infections, capable of causing human to human transmission. This article, based on our experience and guidelines issued by CDC as well as IDA, intends to provide a review of recommended protocols for dental professionals.

O4 Using translational simulation to train novel ‘mobile emergency rapid intubation teams’ during the COVID-19 pandemic

BackgroundThe COVID-19 pandemic resulted in significant numbers of patients requiring intubation and transfer. To achieve this ‘Mobile Emergency Rapid Intubation Teams’ (MERIT) were created. Mindful of individuals working outside of their normal environment, we created a simulation training program to improve clinical care and ensure staff and patient safety.Education ProgrammeThe MERIT call process was simulated in high-fidelity including team brief, preparing equipment, use of personal protective equipment, induction and intubation. An educational video was created for viewing prior to simulation events. Debriefs were conducted after every simulation and MERIT call;multiple issues were raised which facilitated regular guidance updates. Faculty ran daily simulations for five weeks.ResultsPost-training evaluation:•Thirty-nine participants responded•95% attended at least one training session•82% felt that training significantly improved their understanding of MERIT processes•84% and 87% strongly agreed that the training improved teamwork and safety respectively•82% strongly agreed that the training improved standardisation•77% strongly agreed that training left them well-prepared to undertake MERIT calls•Thematic analysis of participant’s reflections showed the following domains were most valuable: practicing processes, correct use of equipment and task management.Patient outcome data:•23 live MERIT calls between 25th March and 5th May 2020•Average time from arrival to intubation was 26min (range 13–36min)•Average time from arrival to departure was 43min (range 27–75min)•Choice of anaesthetic agents was identical in all intubations•3 episodes of desaturation (SpO2 <80%) and 2 episodes of hypotension (Systolic BP <90mmHg)•No other critical incidents reportedDiscussionThe rapid introduction of MERIT necessitated a training programme that simultaneously trained staff and developed processes.1 Intubation of COVID-19 patients exposes clinicians to significant personal risk and this programme sought to mitigate risks by standardising procedures and reinforcing best practice. Feedback suggests that the programme improved teamwork, safety, and confidence of staff caring for critically unwell individuals. Patient outcome data showed intubations were timely and with minimal physiological derangement. This reinforces previous evidence that standardisation can improve outcomes.2ConclusionsIn this programme, translational simulation facilitated training of a large number of clinicians to perform the complex, novel and evolving role of MERIT in a short timeframe. Keeping staff safe was an important positive theme to emerge from the participant survey.RecommendationsTargeted ‘diagnostic’ translation simulation should be considered when introducing a novel service to facilitate rapid learning and development of new models of care.ReferencesBrazil, V. Translational simulation: not ‘where?’ but ‘why?’ A functional view of in situ simulation. Advances in Simulation volume 2, Article number: 20 (2017). https://advancesinsimulation.biomedcentral.com/articles/10.1186/s41077-017-0052-3 (Accessed 18/05/20)McQueen C, et al. Prehospital anaesthesia performed by physician/critical care paramedic teams in a major trauma network in the UK: a 12 month review of practice. Emerg Med J. 2015 Jan;32(1):65-9. https://www.ncbi.nlm.nih.gov/pubmed/24132327 (Accessed 18/05/20).