Cryo-EM Studies of Virus-Antibody Immune Complexes

Abstract

Antibodies play critical roles in neutralizing viral infections and are increasingly used as therapeutic drugs and diagnostic tools. Structural studies on virus-antibody immune complexes are important for better understanding the molecular mechanisms of antibody-mediated neutralization and also provide valuable information for structure-based vaccine design. Cryo-electron microscopy (cryo-EM) has recently matured as a powerful structural technique for studying bio-macromolecular complexes. When combined with X-ray crystallography, cryo-EM provides a routine approach for structurally characterizing the immune complexes formed between icosahedral viruses and their antibodies. In this review, recent advances in the structural understanding of virus-antibody interactions are outlined for whole virions with icosahedral T = pseudo 3 (picornaviruses) and T = 3 (flaviviruses) architectures, focusing on the dynamic nature of viral shells in different functional states. Glycoprotein complexes from pleomorphic enveloped viruses are also discussed as immune complex antigens. Improving our understanding of viral epitope structures using virus-based platforms would provide a fundamental road map for future vaccine development.

SARS-CoV-2 and other human coronaviruses: Mapping of protease recognition sites, antigenic variation of spike protein and their grouping through molecular phylogenetics

“…S-glycoprotein with a metastable perfusion conformation following translation is a typical representative of class I fusion protein. It needs to be activated by proteolytic cleavage at S1/S2 and/or S2’ sites by proteases of the host cell followed by a configuration change in the S2 subunit that facilitates the release of spike fusion peptide to promote the fusion reaction and viral entry ( Hulswit et al 2016 ; Wang et al 2020b ). Therefore, we restricted our search for candidate protease recognition site to a segment of the S-protein starting from 25 amino acid upstream of S1/S2 junction, encompassing the S2 subunit up to 10 amino acid downstream of S2’ site in each of the seven strains of CoVs.…”

“…Moreover, the host proteases that can prime S-protein activation vary among different CoVs. This diversity is a deciding factor for the virus's epidemiological and pathological properties, like host range, tissue tropism, transmissibility, and mortality ( Wang et al 2020b ). S-protein of SARS-CoV-2 possesses a unique multi basic furin cleavage site (−RRAR–) in between the amino acid residues 682 and 685, within the S1/S2 domain ( Fig.…”

“…S-protein of SARS-CoV-2 possesses a unique multi basic furin cleavage site (−RRAR–) in between the amino acid residues 682 and 685, within the S1/S2 domain ( Fig. 1 ), discrete from SARS-CoV and other related CoVs which contain only trypsin or TMPRSS2 cleavage site at R667 ( Wang et al 2020b ). The presence of a similar furin cleavage site has also been reported in MERS-CoV ( Hoffmann et al 2020 ; Millet and Whittaker 2014 ).…”

The Main Molecular and Serological Methods for Diagnosing COVID-19: An Overview Based on the Literature

“…More specifically, the low accuracy of RT-qPCR kits may be less than optimal (i.e., <100%) resulting in the growth of false negative results, especially among asymptomatic patients [ 77 , 78 ]. Studies have shown the high rate of false-negative results in different countries of Asia using the RT-qPCR test [ 47 , 79 ]. A study reported a case of severe COVID-19 with an initial seven consecutive false-negative RT-qPCR results in the First Affiliated Hospital, School of Medicine, Zhejiang University, also in China [ 80 ].…”

Traditional Chinese medicine Lianhua Qingwen for treating COVID-19

“…[ 6 ] In terms of modern pharmacological analysis, the prescription has multiple functions of antiviral, anti-inflammatory, antibacterial, antipyretic, and so on. [ 7 ] It could inhibit SARS-CoV-2 replication, alter the viral morphology, and reduce the cytokine release from host cells. [ 8 ] LHQW has been used for fighting against the COVID-19 that it was clinically shown to have a beneficial effect.…”