CR3022 as A Target for SARS-CoV-2 Antibody Development

The initial cases of novel coronavirus (SARS-CoV-2) pneumonia (NCP) occurred in City Wuhan, Province Hubei, China, in December 2019. Within China, Wuhan has been shut down, with individuals not permitted to leave this city in an effort to contain the coronavirus. For now, a large number of travelers are being isolated for fever and reported a recent history of travelling to Wuhan for triage diagnostic testing.

These immediate efforts resemble what happened with severe acute respiratory syndrome (SARS) in 2002-2003. Both of them belong to the same group of coronavirus, which are enveloped RNA viruses, distributed broadly, and able to cause respiratory disorders. As a well-recognized expert in the antibody market, Creative Biolabs has built neutralizing antibody (nAb) platforms and provides end-to-end antibody development solutions to help global populations to fight against SARS-CoV-2, according to the research from SARS coronavirus (SARS-CoV).

• The Correlation Between SARS-CoV-2 and SARS-CoV

Based on the phylogenetic analysis, SARS-CoV-2 belongs to lineage B betacoronavirus and shares high sequence identity (70% similarity) with that of bat or human SARS-related coronavirus (SARSr-CoV) and bat SARS-like coronavirus (SL-CoV). In initial studies, some potent monoclonal antibodies (mAbs) against SARS-CoV have been identified. These antibodies target the spike protein (S-protein) of SARS-CoV and SL-CoVs, which is a type I transmembrane glycoprotein and capable of mediating the entrance to human respiratory epithelial cells through interacting with angiotensin-converting enzyme 2 (ACE2), a class of cell surface receptor. More specifically speaking, the 193 amino acid length (N318-V510) receptor-binding domain (RBD) within spike protein is the key target for nAbs.

Fig.1 The sequence identity between different coronavirus. (Tian, 2020)

• Recent Findings

Fortunately, Chinese scientists have found out that one of the antibodies identified during SARS can neutralize the coronavirus that induced the pneumonia outbreak in China and several other nations. In their paper, the highlight was that a SARS-CoV specific human mAb, CR3022, could bind potently with the RBD of SARS-CoV-2 (KD of 6.3 nM). The epitope of CR3022 doesn’t overlap with the ACE2 within SARS-CoV-2 RBD. This discovery creates an opportunity that CR3022 compound, combined with other antibodies that can bind to this new virus, would facilitate the first therapeutic strategies for the novel pneumonia and stop the epidemics.

• CR3022 for SARS-CoV-2 Antibody Development

Fig.2 The evidence in SARS-CoV-2 studies. (Tian, 2020)

The person-to-person spread has been confirmed by the investigation that there were 15 medical care personnel infections and a number of family transmission cases, demonstrating the severe infectivity and pathogenicity of SARS-CoV-2. Currently, there is no antiviral treatment or effective vaccine against this viral infection. At Creative Biolabs, we consider that the most direct and simplest approach to combating SARS-CoV-2 may be one to neutralize the coronavirus from entering cells, the reaction that antibodies normally function in our body.

Considering the relatively high identity of RBD in SARS-CoV-2 and SARS-CoV, it is urgent to evaluate the cross reactivity of anti-SARS-CoV antibodies with SARS-CoV-2 spike protein, which is very likely to have significant implications for rapid development of therapeutic nAbs against SARS-CoV-2. As shown in the diagram, the predicted conformation of SARS-CoV-2 RBD and its complex structures with several nAbs are shown, and the modeling results support the interactions between SARS-CoV-2 RBD and certain SARS-CoV antibodies (Fig.2a). This might owe to the relatively high identity (73%) of RBD between SARS-CoV-2 and SARS-CoV (Fig.2b). For example, residues in RBD of SARS-CoV that make polar interactions with a nAb m396 as illustrated by the complex crystal structure are unvaryingly conserved in SARS-CoV-2 RBD (Fig.2c). Consequently, CR3022 has the potential to be considered as candidate therapeutics, alone or in combination with other nAbs, for the prevention and treatment of SARS-CoV-2.

Based on abundant expertise in contagion and sophisticated techniques in the antibody discovery, Creative Biolabs offers time-saving, cost-effective services to select high-quality nAbs with high affinity and specificity. We are pleased to tailor the most appropriate strategies by virtue of CR3022 and to manufacture valuable antibody drugs for worldwide customers against SARS-CoV-2. For more information on antibody development, please directly contact us or consult our technical supports online.

Reference

1. Tian, X.; et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. BioRxiv. 2020: 1-12.

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