Question

How could the specific proteins (S, E, M, and N) on SARS-CoV-2 be useful targets for diagnosis? (1)

For treatment? (1)

What technologies or molecular diagnostics/therapeutics would be useful? (1)

Answer 1

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) belongs to the betacoronavirus class. SARS-CoV-2 is the causative agent of COVID-19 which attacks the lower respiratory tract and causes Pneumonia. The genome consists of glycosylated spike proteins (S) which are involved in the attachment and entry of the host cell by both SARS-CoV and SARS-CoV-2 with the help of angiotensin-converting enzyme 2 (ACE2) found on the surface of the host cell. The initiation of the infection thus starts with the interaction of S protein with the ACE2 receptor and can act as the main target for developing antibody and antiviral kits. The betacoronavirus genome consists of single-stranded RNA which along with S protein consists of the envelope protein (E), membrane glycoprotein (M) and nucleocapsid protein (N). N together with M and E form the assembly of the virion. M protein also interacts with E and S proteins and cause viral budding and release. The N protein acts as an important target for immunohistochemistry and antigen detection in clinical specimens because of its ability to get abundantly expressed in infected cells where mRNA amplification was almost 10 times higher 12 hours post-infection compared to other structural genes. The design of the diagnostic kits and vaccines for the treatment depends on the basic understanding of the structure and function of the various proteins making up the virus assembly.

For treating the SARS-CoV 2 which is completely new with no treatment available, the identification of targets is important to identify the drugs with high target specificity or identify the currently available drugs used to treat other viral diseases. A very classic example of this is that of antiviral drug Arbidol which has entered into clinical trials to treat SARS-CoV-2. Arbidol is used against the influenza virus tbecause its ability to act as a virus-host cell fusion inhibitor thus preventing virus entry into the host cell. This works on the principle of interaction of S protein with ACE 2 receptor which acts as a viable drug target.

The molecular diagnostics/therapeutics that would be useful include- reverse transcription-polymerase chain reaction (RT-PCR) for detection of viral RNA, immunofluorescence assay (IFA) for identification of antibodies induced by a virus and/or enzyme-linked immunosorbent assay (ELISA) for detection of nucleocapsid protein (NP).