Characteristics of SARS-CoV-2 and COVID-19

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named 'coronavirus disease 2019' (COVID-19), which threatens human health and public safety. In this Review, we describe the basic virology of SARS-CoV-2, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses. We summarize current knowledge of clinical, epidemiological and pathological features of COVID-19, as well as recent progress in animal models and antiviral treatment approaches for SARS-CoV-2 infection. We also discuss the potential wildlife hosts and zoonotic origin of this emerging virus in detail.

Fig. 1. Timeline of the key events of the COVID-19 outbreak.

The first recorded cases were reported in December 2019 in Wuhan, China. Over the course of the following 10 months, more than 30 million cases have been confirmed worldwide. COVID-19, coronavirus disease 2019; ICTV, International Committee on Taxonomy of Viruses; PHEIC, public health emergency of international concern; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; WHO, World Health Organization.

Fig. 2. Phylogenetic tree of the full-length genome sequences of SARS-CoV-2, SARSr-CoVs and other betacoronaviruses.

The construction was performed by the neighbour joining method with use of the program MEGA6 with bootstrap values being calculated from 1,000 trees. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clusters with closely related viruses in bats and pangolins and together with SARS-CoV and bat SARS-related coronaviruses (SARSr-CoVs) forms the sarbecoviruses. The sequences were downloaded from the GISAID database and GenBank. MERS-CoV, Middle East respiratory syndrome coronavirus.

Fig. 3. Key differences in the spike protein of SARS-CoV-2 and related coronaviruses.

a | Schematic diagram of the spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. The residue numbers of each region correspond to their positions in the S proteins of SARS-CoV and SARS-CoV-2. The dark blue blocks represent insertions in the S protein. The insertions at amino acids 675–691 of the SARS-CoV-2 S protein are shown in an enlargement at the bottom right and aligned with those of other coronaviruses in the same region. b | Alignment of the receptor-binding domain (RBD) in SARS-CoV-2, SARS-CoV BJ01, RaTG13, pangolin coronavirus reported from Guangdong, China (GD pangolin), pangolin coronavirus reported from Guangxi, China (GX pangolin) and bat SARS-related coronavirus (SARSr-CoV) WIV1. The receptor-binding motif (RBM) is shown in purple, and the five key residues that contact angiotensin-converting enzyme 2 (ACE2) directly are highlighted in green. c | Five critical residues in the RBD of SARS-CoV-2 and other viruses. d | Comparison of the structure of SARS-CoV-2 and SARS-CoV RBD complexed with human ACE2 (hACE2); SARS-CoV-2 RBM in purple, SARS-CoV RBM in yellow and hACE2 in green). Five critical residues that are involved in the RBM–ACE2 binding are shown. The Protein Data Bank codes are 2AJF for SARS-CoV RBD–hACE2 and 6VW1 for SARS-CoV-2 RBD–hACE2. The GenBank entries are AY278488 for SARS-CoV BJ01, MN996532 for the bat SARSr-CoV RaTG13, MT121216 and MT072864 for the GD pangolin and GX pangolin coronaviruses, respectively, and KF367457 for the bat SARSr-CoV WIV1. CP, cytoplasmic domain; FP, fusion peptide; HR1, heptad repeat 1; HR2, heptad repeat 2; NTD, N-terminal domain; SP, signal peptide; TM, transmembrane domain. Parts a and b adapted from ref., Springer Nature Limited.

Fig. 4. Clinical features of COVID-19.

Typical symptoms of coronavirus disease 2019 (COVID-19) are fever, dry cough and fatigue and in severer cases dyspnea. Many infections, in particular in children and young adults, are asymptomatic, whereas older people and/or people with co-morbidities are at higher risk of severe disease, respiratory failure and death. The incubation period is ~5 days, severe disease usually develops ~8 days after symptom onset and critical disease and death occur at ~16 days. ARDS, acute respiratory distress syndrome; ICU, intensive care unit.

Fig. 5. SARS-CoV-2 replication and potential therapeutic targets.

Potential antivirals target the different steps of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, ranging from receptor binding, entry and fusion to replication. Furthermore, immunoglobulin-based and immunomodulatory drugs are potential therapeutics as well. Note that robust data on clinical efficacy are lacking for most of these treatments so far. 3CLpro, 3C-like protease; ACE2, angiotensin-converting enzyme 2; CR3022, a SARS-CoV-specific human monoclonal antibody; E, envelope protein; EK1C4, lipopeptide derived from EK1 which is a pan-coronavirus fusion inhibitor targeting the HR1 domain of the spike protein; ER, endoplasmic reticulum; gRNA, genomic RNA; HR2P, heptad repeat 2-derived peptides of SARS-CoV-2 spike protein; IL-6, interleukin-6; ISG, interferon-stimulated gene; M, membrane protein; RdRp, RNA-dependent RNA polymerases; sgRNA, subgenomic RNA; S, spike protein; TMPRSS2, transmembrane protease serine protease 2.