Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic.

Defining the risk of SARS-CoV-2 variants on immune protection.

The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases within the National Institutes of Health established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants that could potentially affect the transmission, virulence, and resistance to infection- and vaccine-induced immunity. The SAVE programme is a critical data-generating component of the US Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines and therapeutics, and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models and notable findings facilitated by this collaborative approach and identify future challenges. This programme is a template for the response to rapidly evolving pathogens with pandemic potential by monitoring viral evolution in the human population to identify variants that could reduce the effectiveness of countermeasures.

Material Basis and Mechanism of Chansu Injection for COVID-19 Treatment Based on Network Pharmacology and Molecular Docking Technology (preprint)

Background: Coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving disease with no effective drug treatment. Traditional Chinese medicines have been widely used to treat COVID-19 in China. Chansu and its major active constituent, bufalin, exert broad-spectrum antiviral effects. Although the clinical efficacy of Chansu injection for COVID-19 treatment has been confirmed, its mechanism of action remains unclear. Objectives: In this study, we used network pharmacology and molecular docking technology to explore the potential material basis and mechanism of action of Chansu injection for COVID-19 treatment. Methods: The main components of Chansu injection were determined using high-performance liquid chromatography (HPLC). The PharmMapper, SwissTargetPrediction, SEA, and TCMID databases were used to screen for the active ingredients and therapeutic targets of Chansu injection while the OMIM and GeneCards Suite databases were used to search for COVID-19-related targets. The STRING database was used for protein–protein interaction (PPI) network construction and topological analysis while DAVID was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the core targets. Molecular docking of the three Chansu injection components (i.e., cinobufagin, resibufogenin, and bufalin) to angiotensin-converting enzyme II, spike (S) protein, 3CL protease, and RNA-dependent RNA polymerase was also carried out. Results: The three Chansu injection compounds were identified using HPLC. A total of 236 drug-related targets and 16,611 disease-related targets were identified, and 77 common targets were determined through mapping. The PPI mapping results revealed 16 core targets obtained through topological analysis and screening. Further, GO and KEGG pathway enrichment analyses revealed that the PI3K and JAK–STAT signaling pathways are the major pathways regulated by Chansu injection in COVID-19 treatment. The molecular docking results suggest that the three Chansu injection components have high binding energies to the S protein. Conclusions: This study revealed that the potential mechanism of Chansu injection for COVID-19 treatment involves multiple targets and pathways, thereby providing a scientific basis for its clinical application and further research.