Generation and transmission of interlineage recombinants in the SARS-CoV-2 pandemic

1. Download : Download high-res image (161KB)
2. Download : Download full-size image

     

Advances and gaps in SARS-CoV-2 infection models

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to recapitulate COVID-19 demographic variables such as comorbidities and age.

In February of 2020, the World Health Organization (WHO) R&D Blueprint convened a group of experts to develop preclinical models of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Since its inception, the goal of this WHO COVID Modeling group (WHO-COM) has been to accelerate the development of Coronavirus Disease 2019 (COVID-19) vaccines and therapeutics by rapidly sharing data among member scientists worldwide. In addition, concerns were raised at that time about the possibility of vaccine-associated enhanced respiratory disease (VAERD) or antibody-dependent enhancement (ADE) after vaccination or infection. In September of 2020, the WHO-COM published a review on COVID-19 animal models [1], which reflected the state-of-the art at that time, with the vast majority of publications authored by members of the group.Preclinical studies in nonhuman primates (NHPs) of COVID-19 vaccines that are currently being deployed [2–5] proved remarkably predictive of the outcome of clinical efficacy studies. In particular, NHP studies not only predicted high clinical efficacy of these vaccines but also suggested immune correlates of protection. Moreover, preclinical studies accurately predicted that protection against severe pneumonia would be easier to achieve than protection against viral replication in nasal mucosa. These observations confirm the value and importance of the use of animal models for COVID-19.In 2021, with several vaccines rolling out worldwide and the detection of variants of concern (VOCs), the development of preclinical models of SARS-CoV-2 infection and their role in COVID-19 research has entered into a new phase. This paper provides an update from the WHO-COM regarding advances in preclinical models. In particular, we discuss how animal model research has provided insight into VOC pathogenesis and correlates of protection and has helped therapeutic development. Finally, we discuss the current status of VAERD research and the race to develop models that recapitulate COVID-19 demographic variables such as comorbidities and age.     

Insights on cross-species transmission of SARS-CoV-2 from structural modeling

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 31 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic and confirmed cases of cross-species transmission, the question of the extent to which this transmission is possible emerges, as well as what molecular features distinguish susceptible from non-susceptible animal species. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also allow us to predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.     

Factors affecting aerosol SARS-CoV-2 transmission via HVAC systems; a modeling study

The role of heating, ventilation, and air-conditioning (HVAC) systems in the transmission of SARS-CoV-2 is unclear. To address this gap, we simulated the release of SARS-CoV-2 in a multistory office building and three social gathering settings (bar/restaurant, nightclub, wedding venue) using a well-mixed, multi-zone building model similar to those used by Wells, Riley, and others. We varied key factors of HVAC systems, such as the Air Changes Per Hour rate (ACH), Fraction of Outside Air (FOA), and Minimum Efficiency Reporting Values (MERV) to examine their effect on viral transmission, and additionally simulated the protective effects of in-unit ultraviolet light decontamination (UVC) and separate in-room air filtration. In all building types, increasing the ACH reduced simulated infections, and the effects were seen even with low aerosol emission rates. However, the benefits of increasing the fraction of outside air and filter efficiency rating were greatest when the aerosol emission rate was high. UVC filtration improved the performance of typical HVAC systems. In-room filtration in an office setting similarly reduced overall infections but worked better when placed in every room. Overall, we found little evidence that HVAC systems facilitate SARS-CoV-2 transmission; most infections in the simulated office occurred near the emission source, with some infections in individuals temporarily visiting the release zone. HVAC systems only increased infections in one scenario involving a marginal increase in airflow in a poorly ventilated space, which slightly increased the likelihood of transmission outside the release zone. We found that improving air circulation rates, increasing filter MERV rating, increasing the fraction of outside air, and applying UVC radiation and in-room filtration may reduce SARS-CoV-2 transmission indoors. However, these mitigation measures are unlikely to provide a protective benefit unless SARS-CoV-2 aerosol emission rates are high (>1,000 Plaque-forming units (PFU) / min).     

Transformation to telephonic genetic counselling during SARS-CoV-2 pandemic: challenges and suggested protocol in Indian scenario

To combat the dreaded diseases in rice like bacterial blight (BB) and blast, host plant resistance has been advocated as the most suitable and sustainable method. Through the present study, we have successfully incorporated three major BB resistance genes, namely Xa21, xa13 and xa5 into NLR3449, a high yielding, blast resistant, fine-grain type, popular rice variety through marker-assisted backcross breeding. Foreground selection was carried out using polymerase chain reaction based, gene-specific markers, namely pTA248 (Xa21), xa13prom (xa13) and xa5FM (xa5) at each generation of backcrossing, while 127 polymorphic SSR markers spanning on 12 chromosomes were used for background selection and backcrossing was limited to two rounds. At BC₂F₁ generation, a single plant (NLR-87-10) with 89.9% recovery, possessing all the three BB resistance genes was forwarded to BC₂F₂ generation. A solitary BC₂F₂ plant, namely NLR-87-10-106 possessing all the three resistance genes and 96% genome recovery was identified and advanced through selfing until BC₂F₄ generation by adopting pedigree-method of selection. Three best BC₂F₄ lines, possessing high level of resistance against BB and blast, and equivalent or superior to NLR 34449 in terms of yield, grain quality and agro-morphological traits were identified and advanced for multi-location trials.

     

Intranasal vaccination with a lentiviral vector protects against SARS-CoV-2 in preclinical animal models

1. Download : Download high-res image (133KB)
2. Download : Download full-size image

     

Stopping the COVID-19 pandemic in dental offices: A review of SARS-CoV-2 transmission and cross-infection prevention

Due to the essential role of dentists in stopping the COVID-19 pandemic, the purpose of this review is to help dentists to detect any weaknesses in their disinfection and cross-contamination prevention protocols, and to triage dental treatments to meet the needs of patients during the pandemic. We used PRISMA to identify peer-reviewed publications which supplemented guidance from the center for disease control about infection control and guidelines for dentists. Dentists must triage dental treatments to meet the needs of patients during the pandemic. The ongoing pandemic has changed the practice of dentistry forever, the changes make it more cumbersome, time-consuming, and costly due to the possible pathways of transmission and mitigation steps needed to prevent the spread of COVID-19. Dental chairside rapid tests for SARS-CoV-2 are urgently needed. Until then, dentists need to screen patients for COVID-19 even though 75% of people with COVID-19 have no symptoms. Despite the widespread anxiety and fear of the devastating health effects of COVID-19, only 61% of dentists have implemented a change to their treatment protocols. As an urgent matter of public health, all dentists must identify the additional steps they can take to prevent the spread of COVID-19. The most effective steps to stop the pandemic in dental offices are to; vaccinate all dentists, staff, and patients; triage dental treatments for patients, separate vulnerable patients, separate COVID-19 patients, prevent cross-contamination, disinfect areas touched by patients, maintain social distancing, and change personal protective equipment between patients.     

Molecular architecture and dynamics of SARS-CoV-2 envelope by integrative modeling

1. Download : Download high-res image (306KB)
2. Download : Download full-size image

     

Dalbavancin binds ACE2 to block its interaction with SARS-CoV-2 spike protein and is effective in inhibiting SARS-CoV-2 infection in animal models

Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a pandemic worldwide.Currently,however,no effective drug or vaccine is avai...     

SARS-CoV-2 lineage B.6 was the major contributor to early pandemic transmission in Malaysia

Malaysia had 10,219 confirmed cases of COVID-19 as of September 20, 2020. About 33% were associated with a Tablighi Jamaat religious mass gathering held in Kuala Lumpur between February 27 and March 3, 2020, which drove community transmission during Malaysia’s second wave. We analysed genome sequences of SARS-CoV-2 from Malaysia to better understand the molecular epidemiology and spread. We obtained 58 SARS-CoV-2 whole genome sequences from patients in Kuala Lumpur and performed phylogenetic analyses on these and a further 57 Malaysian sequences available in the GISAID database. Nine different SARS-CoV-2 lineages (A, B, B.1, B.1.1, B.1.1.1, B.1.36, B.2, B.3 and B.6) were detected in Malaysia. The B.6 lineage was first reported a week after the Tablighi mass gathering and became predominant (65.2%) despite being relatively rare (1.4%) globally. Direct epidemiological links between lineage B.6 viruses and the mass gathering were identified. Increases in reported total cases, Tablighi-associated cases, and community-acquired B.6 lineage strains were temporally linked. Non-B.6 lineages were mainly travel-associated and showed limited onward transmission. There were also temporally correlated increases in B.6 sequences in other Southeast Asian countries, India and Australia, linked to participants returning from this event. Over 95% of global B.6 sequences originated from Asia Pacific. We also report a nsp3-C6310A substitution found in 47.3% of global B.6 sequences which was associated with reduced sensitivity using a commercial diagnostic real-time PCR assay. Lineage B.6 became the predominant cause of community transmission in Malaysia after likely introduction during a religious mass gathering. This event also contributed to spikes of lineage B.6 in other countries in the Asia-Pacific. Mass gatherings can be significant causes of local and global spread of COVID-19. Shared genomic surveillance can be used to identify SARS-CoV-2 transmission chains to aid prevention and control, and to monitor diagnostic molecular assays.Clinical Trial Registration: COVID-19 paper.     

Glycogen synthase kinase-3: A putative target to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic

The coronavirus disease 19 (COVID-19) outbreak caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) had turned out to be highly pathogenic and transmittable. Researchers throughout the globe are still struggling to understand this strain's aggressiveness in search of putative therapies for its control. Crosstalk between oxidative stress and systemic inflammation seems to support the progression of the infection. Glycogen synthase kinase-3 (Gsk-3) is a conserved serine/threonine kinase that mainly participates in cell proliferation, development, stress, and inflammation in humans. Nucleocapsid protein of SARS-CoV-2 is an important structural protein responsible for viral replication and interferes with the host defence mechanism by the help of Gsk-3 protein. The viral infected cells show activated Gsk-3 protein that degrades the Nuclear factor erythroid 2-related factor (Nrf2) protein, resulting in excessive oxidative stress. Activated Gsk-3 also modulates CREB-DNA activity, phosphorylates NF-​κB, and degrades β-catenin, thus provokes systemic inflammation. Interaction between these two pathophysiological events, oxidative stress, and inflammation enhance mucous secretion, coagulation cascade, and hypoxia, which ultimately leads to multiple organs failure, resulting in the death of the infected patient. The present review aims to highlight the pathogenic role of Gsk-3 in viral replication, initiation of oxidative stress, and inflammation during SARS-CoV-2 infection. The review also summarizes the potential Gsk-3 pathway modulators as putative therapeutic interventions in combating the COVID-19 pandemic.