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Published: 30 April 2020

Reprinted for educational purposes and social benefit, not for profit.


The outbreak of COVID-19, the disease caused by infection of the coronavirus SARS-CoV-2 that began in December 2019 in Wuhan, China, has caused more than 2 990 559 confirmed human infections and 207 446 deaths as of 27 April 2020 (Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University). Scientists are working quickly on multiple aspects of the pandemic. Genetic analyses are conducted to reveal the source and evolution of SARS-CoV-2, providing knowledge that can be used to contain it and to avoid future outbreaks. Epidemiological studies that incorporate lessons learned from outbreaks of previous related viral diseases can guide the development of public health measures effective to contain the current and future outbreaks. Basic virology studies reveal viral structure and function. Pathology studies inform the development of strategies to interfere with infection. COVID-19 prevention and treatment strategies are being developed in preclinical and clinical studies. Antibody-based therapy is one viable treatment option. Here, we discuss some of the most active areas of developing strategies to treat COVID-19, focusing on the approaches to generate neutralizing antibodies against SARS-CoV-2 for prophylactic and therapeutic treatment of COVID-19.

SARS-CoV-2 structures, life cycle, and inhibition strategies of virus replication. (A) The virus particle structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spherical particle of SARS-CoV-2 consists of four structural proteins, including the spike proteins (S), the membrane protein (M), the envelope protein (E), and the nucleocapsid (N). The S, M, and E proteins are incorporated in the virus membrane, and the N protein is inside the particle and associated with virus genomic RNA. (B) The single-stranded positive-sense RNA genome of SARS-CoV-2. The ORF1a, or the ORF1a and ORF1b together, encodes the large polyproteins pp1a and pp1ab. The two polyproteins are further cleaved into 16 nonstructural proteins (nsp1–nsp16). The papain-like protease (PLpro), the 3C-like protease (3CLpro), the RNA-dependent RNA polymerase (RdRp), and the exonuclease (ExoN) are indicated. In addition to the nonstructural and structural proteins, the genome of SARS-CoV-2 also encodes six accessory proteins. (C) The structure of spike protein. The spike protein is a trimer and each monomer comprises an N-terminal S1 subunit and a C-terminal S2 subunit. The S1 subunit is further divided into the N-terminal domain (NTD), the receptor-binding domain (RBD), subdomain 1 (SD1), and subdomain 2 (SD2). The S2 subunit is further divided into the fusion peptide (FP), the heptad repeat 1 (HR1), and heptad repeat 2 (HR2). During virus entry, S1 is responsible for receptor binding, and S2 is responsible for membrane fusion. (B) and (C) Were not drawn proportionally to their genome sizes. (D) The life cycle of SARS-CoV-2 and inhibition of virus replication with different strategies. Upon binding to the cellular receptor angiotensin-converting enzyme 2 (ACE2), the spike protein is activated by protease cleavage, such as TMPRSS2. After membrane fusion, the genomic RNA is released into the cytoplasm. The ORF1a and ORF1ab are translated into pp1a and pp1ab, which are cleaved by PLpro and 3CLpro to produce nonstructural proteins. Several nsps, including nsps 7–10, nsp12, and nsp14, form the replication–transcription machinery to produce genomic and subgenomic RNAs. After the translation of structural proteins, the virion is assembled at the ER-Golgi intermediate compartment (ERGIC) and encapsidate the N protein and genomic RNA. The mature virion is released outside of cells by transportation through the vesicles. Virus replication at the steps of entry, proteolysis, and genome replication can be inhibited as indicated