Virus World

The COVID-19 pandemic has affected hundreds of millions of individuals and caused more than six million deaths. The prolonged pandemic duration and the continual inter-individual transmissibility have contributed to the emergence of a wide variety of SARS-CoV-2 variants. Genomic surveillance and phylogenetic studies have shown that substantial mutations in crucial supersites of spike glycoprotein modulate the binding affinity of the evolved SARS-COV-2 lineages to ACE2 receptors and modify the binding of spike protein with neutralizing antibodies.

The immunological spike mutations have been associated with differential transmissibility, infectivity, and therapeutic efficacy of the vaccines and the immunological therapies among the new variants. This review highlights the diverse genetic mutations assimilated in various SARS-CoV-2 variants. The implications of the acquired mutations related to viral transmission, infectivity, and COVID-19 severity are discussed. This review also addresses the effectiveness of human neutralizing antibodies induced by SARS-CoV-2 infection or immunization and the therapeutic antibodies against the ascended variants.

Published March 30, 2024:

https://doi.org/10.1007/s15010-024-02223-y 

LA JOLLA, CA-;Researchers at La Jolla Institute for Immunology (LJI) have found that Zika virus can mutate to become more infective-;and potentially break through pre-existing immunity.  "The world should monitor the emergence of this Zika virus variant," says LJI Professor Sujan Shresta, Ph.D., who co-led the Cell Reports study with Professor Pei-Yong Shi, Ph.D., of the University of Texas Medical Branch (UTMB). Zika virus is carried by mosquitoes, and the symptoms of Zika infection are usually mild in adults. However, the virus can infect a developing fetus, resulting in birth defects such as microcephaly. Zika virus and dengue virus overlap in many countries worldwide. Like Zika, dengue virus is a mosquito-borne flavivirus, and thus shares many biological properties. In fact, the viruses are similar enough that the immune response sparked by prior dengue exposure can offer protection against Zika.  Unfortunately, both viruses are also quick to mutate. "Dengue and Zika are RNA viruses, which means they can change their genome," explains Shresta. "When there are so many mosquitoes and so many human hosts, these viruses are constantly moving back and forth and evolving.

To study Zika's fast-paced evolution, the LJI team recreated infection cycles that repeatedly switched back and forth between mosquito cells and mice. This work gave the LJI scientists a window into how Zika virus naturally evolves as it encounters more hosts. The researchers found it is relatively easy for Zika virus to acquire a single amino acid change that allows the virus to make more copies of itself-;and help infections take hold more easily. This mutation (called NS2B I39V/I39T mutation) boosts the virus's ability to replicate in both mice and mosquitoes. This Zika variant also showed increased replication in human cells.  "This single mutation is sufficient to enhance Zika virus virulence," says study first author Jose Angel Regla-Nava, Ph.D., former postdoctoral researcher at LJI and current Associate Professor at the University of Guadalajara, Mexico. "A high replication rate in either a mosquito or human host could increase viral transmission or pathogenicity-;and cause a new outbreak." Adds Shresta, "The Zika variant that we identified had evolved to the point where the cross-protective immunity afforded by prior dengue infection was no longer effective in mice.

Unfortunately for us, if this variant becomes prevalent, we may have the same issues in real life." So how can we prepare for this kind of variant? Shresta's laboratory is already looking at ways to tailor Zika vaccines and treatments that counteract this dangerous mutation. She will also continue to work closely with Regla-Nava to better understand exactly how this mutation helps Zika replicate more efficiently. "We want to understand at what point in the viral life cycle this mutation makes a difference," says Shresta.

Research cited published in Cell Reports (April 12, 2022):

https://doi.org/10.1016/j.celrep.2022.110655 

The new strain may be growing faster in some parts of the country, Health Secretary tells MPs. Health Secretary Matt Hancock said at least 60 different local authorities had recorded Covid infections caused by the new variant. He said the World Health Organization had been notified and UK scientists were doing detailed studies. He said there was "nothing to suggest" it caused worse disease or that vaccines would no longer work. He told MPs in the House of Commons that over the last week, there had been sharp, exponential rises in coronavirus infections across London, Kent, parts of Essex and Hertfordshire. "We've currently identified over 1,000 cases with this variant predominantly in the South of England although cases have been identified in nearly 60 different local authority areas. "We do not know the extent to which this is because of the new variant but no matter its cause we have to take swift and decisive action which unfortunately is absolutely essential to control this deadly disease while the vaccine is rolled out." 

EG.5.1 is a subvariant of the SARS-CoV-2 Omicron XBB variant that is rapidly increasing in prevalence worldwide. EG.5.1 has additional substitutions in its spike protein (namely, Q52H and F456L) compared with XBB.1.5. However, the pathogenicity, transmissibility, and immune evasion properties of clinical isolates of EG.5.1 are largely unknown. In this study, we used wild-type Syrian hamsters to investigate the replicative ability, pathogenicity, and transmissibility of a clinical EG.5.1 isolate. Our data show that there are no obvious differences in growth ability and pathogenicity between EG.5.1 and XBB.1.5, and both EG.5.1 and XBB.1.5 are attenuated compared to a Delta variant isolate. We also found that EG.5.1 is transmitted more efficiently between hamsters compared with XBB.1.5.

In addition, unlike XBB.1.5, we detected EG.5.1 virus in the lungs of four of six exposed hamsters, suggesting that the virus tropism of EG.5.1 is different from that of XBB.1.5 after airborne transmission. Finally, we assessed the neutralizing ability of plasma from convalescent individuals and found that the neutralizing activity against EG.5.1 was slightly, but significantly, lower than that against XBB.1.5 or XBB.1.9.2. This suggests that EG.5.1 effectively evades humoral immunity and that the amino acid differences in the S protein of EG.5.1 compared with that of XBB.1.5 or XBB.1.9.2 (i.e., Q52H, R158G, and F456L) alter the antigenicity of EG.5.1. Our data suggest that the increased transmissibility and altered antigenicity of EG.5.1 may be driving its increasing prevalence over XBB.1.5 in the human population.

Available as preprint in bioRxiv (Sept 1 2023):

https://doi.org/10.1101/2023.08.31.555819 

Several Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) neutralising monoclonal antibodies (mAbs) have received emergency use authorisation by regulatory agencies for treatment and prevention of Coronavirus Disease 2019 (COVID-19), including in patients at risk for progression to severe disease. Here we report the persistence of viable SARS-CoV-2 in patients treated with sotrovimab and the rapid development of spike gene mutations that have been shown to confer high level resistance to sotrovimab in vitro. We highlight the need for SARS-CoV-2 genomic surveillance in at risk individuals to inform stewardship of mAbs use and prevent potential treatment failures.

Preprint available in medRxiv (Dec. 21, 2021):

https://doi.org/10.1101/2021.12.18.21267628