Publications by authors named "Guangkuo Guan"

2 Publications

  • Page 1 of 1

Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes.

PLoS Biol 2021 05 7;19(5):e3001209. Epub 2021 May 7.

MOE Key Laboratory of Protein Science & Collaborative Innovation Center of Biotherapy, School of Medicine, Tsinghua University, Beijing, China.

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) threatens global public health and economy unprecedentedly, requiring accelerating development of prophylactic and therapeutic interventions. Molecular understanding of neutralizing antibodies (NAbs) would greatly help advance the development of monoclonal antibody (mAb) therapy, as well as the design of next generation recombinant vaccines. Here, we applied H2L2 transgenic mice encoding the human immunoglobulin variable regions, together with a state-of-the-art antibody discovery platform to immunize and isolate NAbs. From a large panel of isolated antibodies, 25 antibodies showed potent neutralizing activities at sub-nanomolar levels by engaging the spike receptor-binding domain (RBD). Importantly, one human NAb, termed PR1077, from the H2L2 platform and 2 humanized NAb, including PR953 and PR961, were further characterized and subjected for subsequent structural analysis. High-resolution X-ray crystallography structures unveiled novel epitopes on the receptor-binding motif (RBM) for PR1077 and PR953, which directly compete with human angiotensin-converting enzyme 2 (hACE2) for binding, and a novel non-blocking epitope on the neighboring site near RBM for PR961. Moreover, we further tested the antiviral efficiency of PR1077 in the Ad5-hACE2 transduction mouse model of COVID-19. A single injection provided potent protection against SARS-CoV-2 infection in either prophylactic or treatment groups. Taken together, these results shed light on the development of mAb-related therapeutic interventions for COVID-19.
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http://dx.doi.org/10.1371/journal.pbio.3001209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133496PMC
May 2021

White spot syndrome virus VP12 interacts with adenine nucleotide translocase of Litopenaeus vannamei.

J Invertebr Pathol 2014 May 4;118:28-33. Epub 2014 Mar 4.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, PR China. Electronic address:

White spot syndrome virus VP12 contains cell attachment motif RGD which is considered to be critical for host cell binding. Until now, the function of this protein remains undefined. In this study, we explored the interaction of VP12 with host cells. A new shrimp protein (adenine nucleotide translocase of Litopenaeus vannamei, LvANT) is selected by far-western overlay assay. Tissue distribution of adenine nucleotide translocase mRNA showed that it was commonly spread in all the tissues detected. Cellular localization of LvANT in shrimp hemocytes showed that it was primarily located in the cytoplasm of hemocytes and colocalized with mitochondria. ELISA and far-western blot assay confirmed that VP12 interacted with LvANT. In vivo neutralization assay showed that anti-LvANT antibody can significantly reduce the mortality of shrimp challenged by WSSV at 48h post-treatment. Our results collectively showed that VP12 is involved in host cell binding via interaction with adenine nucleotide translocase.
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http://dx.doi.org/10.1016/j.jip.2014.02.006DOI Listing
May 2014