COVID-19: Chinese cocktail therapy blocks the virus invasion
COVID-19: Chinese cocktail therapy blocks the virus invasion. The Chinese medical team of Li Lanjuan/Wang Xiangxi/Zhu Fengcai, etc. jointly developed a highly effective COVID-19 cocktail therapy to better block the virus invasion.
Recently, researcher Wang Xiangxi of the Institute of Biophysics of the Chinese Academy of Sciences, Academician Li Lanjuan of the First Affiliated Hospital of Zhejiang University, and others used “Rational Development of a Human Antibody Cocktail that Deploys Multiple Functions to Confer Pan-SARS-CoVs Protection” on the research of the COVID-19 neutralizing antibody combination. And “Structure-based development of human antibody cocktails against SARS-CoV-2” were published online in Cell Research magazine.
These two studies successfully screened a cocktail of antibodies against SARS-CoV-2 and SARS-CoV with high neutralization ability, and revealed the potential synergistic mechanism of their combined antibodies. On the basis of a humanized monoclonal antibody H014 (Lv, Z. et al., Science, 2020) that was screened by our team that has a broad-spectrum neutralizing effect on the β family of coronaviruses, a reasonable NAb screening strategy was applied. , Found a highly effective new coronavirus-specific neutralizing antibody P17, which can play an effective protective role in animal models.
(Fig1. Characterization of H014’s candidate combination NAb P17)
Functional data indicate that P17 can block the interaction between SARS-CoV-2RBD and the receptor ACE2 and block the viral membrane fusion process. Further research found that the antibody combination of H014 and P17 can effectively improve the neutralization ability of SARS-CoV-2 and can effectively neutralize the SARS pseudovirus. At the same time, the addition of low concentration H014 antibody can enhance the ability of P17 antibody to inhibit membrane fusion. The H014 antibody alone cannot inhibit the membrane fusion process. In addition, in an established SARS-CoV-2 based mouse model, the cocktail combination of P17 and H014 can increase the protective efficacy of a single antibody by 3 to 10 times.
(Fig2.P17’s preventive and therapeutic effects)
The above research reveals the molecular basis of the antibody cocktail to synergistically neutralize SARS-CoV-2, and provides a theoretical basis for the further development of COVID-19 multi-antibody cocktail therapy.
The research team also screened and obtained the neutralizing antibody FC05 against NTD, and combined FC05 with three RBD neutralizing antibodies H014, P17, HB27, and analyzed SARS-CoV through cryo-electron microscopy imaging single particle three-dimensional reconstruction technology The high-resolution three-dimensional structure of the combination of -2 S trimer and three cocktail antibodies provides a reasonable explanation for the synergistic effect of the combined antibodies from the perspective of structural biology. At the same time, based on the binding mode of the two antibodies, the study also proposed the design of bivalent antibodies, which can further prevent the conformational changes of the new coronavirus S protein in binding to ACE2, thereby better blocking virus invasion.
(Fig3.: The structural basis of synergy in antibody mixtures)
The study finally summarized the advantages of the combination of two antibodies for antibody cocktail therapy, and analyzed the neutralizing antibody epitopes of the current structural analysis, and screened out three non-competitive epitope antibodies or even four antibodies that were used as antibodies at the same time The possible combinations of cocktail therapy provide more theoretical basis for designing antibody cocktail therapy based on structural information and enhancing the synergy of antibodies.