The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is still spreading, with devastating consequences for human life and global economic mortality and morbidity. SARS-CoV-2 is transmitted between infected and uninfected people through unprotected close contact with pollutants and droplets. Current studies have shown that the most common manifestations of COVID-19 are respiratory symptoms such as fever, dry cough and even dyspnea. Severe cases are reported to show sepsis, secondary infection and organ failure. COVID-19 is the third new acute infectious coronavirus disease after SARS-CoV and MERS-CoV in the past 20 years, which shows that coronavirus still poses a strong threat to public health.
Schematic diagrams of the SARS-CoV-2 virus particle and genome. (Signal Transduction and Targeted Therapy)
SARS-CoV-2 is a single-stranded sense RNA (+ssRNA) virus, which belongs to the β coronavirus family. The genome size of the newly sequenced SARS-CoV-2 is ~29.9kb, and the homology with SARS-CoV is ~78%. The genomic RNA of SARS-CoV-2 consists of two main open reading frames (orf), ORF1a and ORF1b, which are translated into pp1a and pp1b proteins. The virus genome encodes 2 cysteine proteases, a papain-like protease (PLpro), or nsp3, and a 3C-like protease (3CLpro), or nsp5. These proteases cleave pp1a and pp1b peptides into 16 non-structural proteins. The core of RNA-dependent RNA polymerase (RdRp) is nsp12, which is a key component of coronavirus replication and transcription. Nsp7 and nsp8 significantly increased the binding of nsp12 to template primer RNA. It is worth noting that RdRp is one of the most promising drug targets identified so far. The rest of the genome has overlapping orf, which encodes four main structural proteins, including S protein (spike glycoprotein), N protein (nucleocapsid protein), M protein (membrane protein) and E protein (envelope protein) and some auxiliary proteins. SARS-CoV-2 also encodes accessory proteins, including ORF3, ORF6, ORF7a, ORF7b, ORF8 and ORF9b, which are all distributed in structural genes.
In the context of the current COVID-19 pandemic, extreme measures have been taken to develop effective prevention and treatment strategies. Efforts are under way to shorten the research time of antiviral drugs such as convalescent plasma, vaccines and neutralizing antibodies. In particular, it has been reported that convalescent plasma may be a treatment for COVID-19. COVID-19 hospitalized patients with convalescent plasma transfusion had a lower mortality rate than patients who received standard treatment. Worldwide, the development of SARS-CoV- 2 vaccines is also accelerating. Fortunately, some mRNA and inactivated vaccines have been reported to have clinical protective effects and are currently available through global emergency approval of vaccines to stop the spread of COVID-19. Because of its good neutralization efficiency and the ability to expand production scale, neutralizing antibodies may become a potential treatment for COVID-19. Many studies have reported that a variety of antibodies against receptor-binding domain (RBD) have been screened and showed strong neutralizing activity in vitro and animal models. So far, many neutralizing antibodies have been clinically evaluated. In addition, peptides extracted from HR1 and HR2 of S protein have been found to have antiviral activity.