Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease caused by a novel coronavirus, SARS-coronavirus (SARS-CoV). The SARS-CoV spike (S) protein is composed of two subunits; the S1 subunit contains a receptor-binding domain that engages with the host cell receptor angiotensin-converting enzyme 2 and the S2 subunit mediates fusion between the viral and host cell membranes. The S protein plays key parts in the induction of neutralizing-antibody and T-cell responses, as well as protective immunity, during infection with SARS-CoV. In this Review, we highlight recent advances in the development of vaccines and therapeutics based on the S protein. SARS-CoV is an enveloped, single and positive-stranded RNA virus2. Its genome RNA encodes a non-structural replicase polyprotein and structural proteins, including spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins3-5. SARS-CoV, a zoonotic virus, resides in hosts that form its natural reservoir, such as bats, but can also infect intermediate hosts, such as small animals (for example, palm civets), before being transmitted to humans6-8. SARS-CoV can infect and replicate in several cell types in the human body and causes serious pathological changes Zoonotic virusA virus that normally exists in vertebrate animals, but can also be transmitted to humans and can cause disease in both animals and humans. Box 1 Pathology of SARS and the life cycle of SARS-CoV infectionSevere acute respiratory syndrome-coronavirus (SARS-CoV) spreads primarily through droplets (respiratory secretions) and close person-to-person contact. After the virus enters into the body, it binds to primary target cells that express abundant virus receptor, the angiotensin-converting enzyme 2 (ACE2), including pneumocytes and enterocytes in the respiratory system. The virus enters and replicates in these cells. The matured virions are then released to infect new target cells121 (FIG. 1). SARS-CoV can also infect mucosal cells of intestines, tubular epithelial cells of kidneys, epithelial cells of renal tubules, cerebral neurons and immune cells122,123. Infectious viral particles in patients with SARS can be excreted through respiratory secretions, stool, urine and sweat. SARS-CoV infection damages lung tissues owing to elevated levels of production and activation of proinflammatory chemokines and cytokines124, resulting in atypical pneumonia with rapid respiratory deterioration and failure.Neutralizing antibodies and/or T-cell immune responses can be raised directly against several SARS-CoV proteins21-23, but mainly target the S protein20,24-26, suggesting that S protein- Structure of the SARS-CoV S proteinThe spikes of SARS-CoV are composed of trimers of S protein, which belongs to a group of class I viral fusion glycoproteins that also includes HIV glyco-protein 160 (Env), influenza haemagglutinin (HA), paramyxovirus F and Ebola virus glycoprotein28. The SARS-CoV S protein encodes a surface glycoprotein precursor that is predicted to be 1,255 amino acids in l...

The outbreak of Coronavirus Disease 2019 has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV spike (S) protein plays the most important roles in viral attachment, fusion and entry, and serves as a target for development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells. SARS-CoV RBD-specific antibodies could crossreact with SARS-CoV-2 RBD protein, and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection.

The ongoing COVID-19 pandemic has prioritized the development of small animal models for SARS-CoV-2. Herein, we adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (termed MASCp6) showed increased infectivity in mouse lung, and led to interstitial pneumonia and inflammatory responses in both young and aged mice following intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion.Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC 50 of 24.86 μg/mL and IC 50 of 15.16 μg/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85×10 -7 M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.