Question

What is known about the mechanism of infection by SARs–CoV-2, in particular, what do we know about the cellular proteins involved? Focus on protein biochemistry. Need a good answer

Answer 1

This scientific brief provides an overview of the modes of transmission of SARS-CoV-2, what is known about when infected people transmit the virus, and the implications for infection prevention and control precautions within and outside health facilities. This scientific brief is not a systematic review. Rather, it reflects the consolidation of rapid reviews of publications in peer-reviewed journals and of non-peer-reviewed manuscripts on pre-print servers, undertaken by WHO and partners. Preprint findings should be interpreted with caution in the absence of peer review. This brief is also informed by several discussions via teleconferences with the WHO Health Emergencies Programme ad hoc Experts Advisory Panel for IPC Preparedness, Readiness and Response to COVID-19, the WHO ad hoc COVID-19 IPC Guidance Development Group (COVID-19 IPC GDG), and by review of external experts with relevant technical backgrounds.

The overarching aim of the global Strategic Preparedness and Response Plan for COVID-19(1) is to control COVID-19 by suppressing transmission of the virus and preventing associated illness and death. Current evidence suggests that SARS-CoV-2, the virus that causes COVID-19, is predominantly spread from person-to-person. Understanding how, when and in what types of settings SARS-CoV-2 spreads is critical to develop effective public health and infection prevention and control measures to break chains of transmission.

Modes of transmission

This section briefly describes possible modes of transmission for SARS-CoV-2, including contact, droplet, airborne, fomite, fecal-oral, bloodborne, mother-to-child, and animal-to-human transmission. Infection with SARS-CoV-2 primarily causes respiratory illness ranging from mild disease to severe disease and death, and some people infected with the virus never develop symptoms.

Contact and droplet transmission

Transmission of SARS-CoV-2 can occur through direct, indirect, or close contact with infected people through infected secretions such as saliva and respiratory secretions or their respiratory droplets, which are expelled when an infected person coughs, sneezes, talks or sings.(2-10) Respiratory droplets are >5-10 μm in diameter whereas droplets <5μm in diameter are referred to as droplet nuclei or aerosols.(11) Respiratory droplet transmission can occur when a person is in close contact (within 1 metre) with an infected person who has respiratory symptoms (e.g. coughing or sneezing) or who is talking or singing; in these circumstances, respiratory droplets that include virus can reach the mouth, nose or eyes of a susceptible person and can result in infection. Indirect contact transmission involving contact of a susceptible host with a contaminated object or surface (fomite transmission) may also be possible (see below).

Airborne transmission

Airborne transmission is defined as the spread of an infectious agent caused by the dissemination of droplet nuclei (aerosols) that remain infectious when suspended in air over long distances and time.(11) Airborne transmission of SARS-CoV-2 can occur during medical procedures that generate aerosols (“aerosol generating procedures”).(12) WHO, together with the scientific community, has been actively discussing and evaluating whether SARS-CoV-2 may also spread through aerosols in the absence of aerosol generating procedures, particularly in indoor settings with poor ventilation.

The physics of exhaled air and flow physics have generated hypotheses about possible mechanisms of SARS-CoV-2 transmission through aerosols.(13-16) These theories suggest that 1) a number of respiratory droplets generate microscopic aerosols (<5 µm) by evaporating, and 2) normal breathing and talking results in exhaled aerosols. Thus, a susceptible person could inhale aerosols, and could become infected if the aerosols contain the virus in sufficient quantity to cause infection within the recipient. However, the proportion of exhaled droplet nuclei or of respiratory droplets that evaporate to generate aerosols, and the infectious dose of viable SARS-CoV-2 required to cause infection in another person are not known, but it has been studied for other respiratory viruses.

Enveloped viruses have evolved membrane glycoproteins (GPs) that mediate entry into host cells. These proteins are important targets for antiviral therapies and vaccines. Several efforts to understand and combat infection by severe acute respiratory syndrome coronavirus (SARS-CoV) have therefore focused on the viral GP, known as spike (S). In a short period of time, important aspects of SARS-CoV S-protein function were unraveled. The identification of angiotensin-converting enzyme 2 (ACE2) as a receptor for SARS-CoV provided an insight into viral tropism and pathogenesis, whereas mapping of functional domains in the S-protein enabled inhibitors to be generated. Vaccines designed on the basis of SARS-CoV S-protein were shown to be effective in animals and consequently are attractive candidates for vaccine trials in humans. Here, we discuss how SARS-CoV S facilitates viral entry into target cells and illustrate current approaches that are used to inhibit this process.