SARS-CoV

What is SARS-CoV?

Coronavirinae is a virus in the family Coronaviridae, which belongs to the order Nidovirales. Coronavirus is a virus that typically affects the respiratory tract of mammals, including humans. Coronaviruses get their name from the canopy-like protrusions on their surface. They have been linked to the common cold, pneumonia, and severe acute respiratory syndrome (SARS) and can also affect the gut. As a result, SARS-CoV is the coronavirus (CoV) that causes severe acute respiratory syndrome (SARS), including 2019-nCoV (also known as SARS-CoV-2), which is seriously harmful and can cause severe pneumonia and even death.

Classification of SARS CoV

Coronaviruses get their name from the canopy-like spines on their surface. There are four main subgroups of coronaviruses, namely α, β, γ, and δ. The seven coronaviruses that can infect humans include four common human coronaviruses: 229E (α coronavirus), NL63 (α coronavirus), OC43 (β coronavirus), HKU1 (β coronavirus), and three other human coronaviruses: MERS-CoV (the β coronavirus that causes Middle East respiratory syndrome (MERS)), SARS-CoV (the β coronavirus that causes severe acute respiratory syndrome (SARS), 2019 novel coronavirus (2019-nCoV, β coronavirus).

SARS CoV structure

Coronaviruses (CoV) have a single-stranded, non-segmental positive polarity RNA genome with four major structural proteins: nucleocapsid (N) protein, transmembrane (M) protein, envelope (E) protein, and spike (S) protein (Fig.1).

SARS-CoV proteins

For some coronaviruses, a complete collection of four structural proteins is not necessary to form a complete, infectious virus. Some additional proteins may be encoded, with overlapping compensating functions. The N protein is the only protein that forms a nucleocapsid and binds primarily to the coronavirus RNA genome. N protein is involved in viral genome-related processes, and it plays an important role in viral RNA replication and host cellular response to viral infection. M proteins support assembly by interacting with viral ribonucleoproteins (RNPs) and S glycoproteins at the budding site and by establishing an M-M interaction network that is able to exclude some host membrane proteins from the viral envelope. The E protein is abundantly expressed in infected cells during the replication cycle, but only a small fraction is incorporated into the viral envelope. Most proteins localize to the ER, the Golgi apparatus, and the ER-Golgi intermediate compartment, which is the intracellular transport site where it is involved in the assembly and initiation of CoV. Changes in S glycoprotein are the main cause of changes in coronavirus host species and tissue orientation. This S glycoprotein is a type 1 membrane glycoprotein with distinct functional domains near the amino (S1) and carboxyl (S2) terminities.

Fig.1 Distribution diagram of coronavirus particle and S protein gene. (Yu Fei, et al., 2020)

SARS-CoV genome

Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome packaged by nucleocapsid phosphoproteins. Coronaviruses are one of the largest RNA viruses, with SARS-CoV-2 genomes ranging from 29.8-29.9 kb and 79.6% and 50% homology to SARS-CoV and MERS, respectively. The SARS-CoV genome consists of 14 open reading frames (ORFs) encoding 27 proteins. The first ORFs (ORF1a and ORF1b) represent nearly 70% of the viral genome and contain 15 non-structural proteins (NSPs). The remaining ORFs at the 3'-end encode 4 structural proteins, namely membrane (M), envelope (E), spike (S), and nucleocapsid (N) proteins, and 8 accessory proteins.

SARS CoV test

ARS-CoV testing methods include molecular diagnostics, antigen tests, and antibody tests. Molecular diagnostics typically use reverse transcription-polymerase chain reaction (RT-PCR) technology for early diagnosis and monitoring by detecting viral nucleic acids in patient samples. This method has high sensitivity and specificity and is the standard commonly used in clinical practice. Antigen tests can quickly identify infected people by detecting viral proteins, and their advantage is that results are quickly available and are suitable for large-scale screening, but they may be less sensitive than RT-PCR. Antibody testing is used primarily for epidemiological studies and to evaluate vaccine efficacy by detecting specific immune responses (IgM and IgG antibodies) to determine whether there is an immune response from previous infection or vaccination. These methods play an important role in clinical diagnosis and public health management.

SARS CoV treatment

SARS-CoV vaccine

At present, the vaccines developed by SARS-CoV are mainly SARS-CoV-2 vaccines, and there are a variety of SARS-CoV-2 vaccines that have been approved for use or are in the research and development stage, including the following types:

mRNA vaccines: Produced by Pfizer/BioNTech and Moderna, they encode the viral spike protein through mRNA to induce an immune response.

Adenovirus vector vaccines, such as AstraZeneca and Johnson & Johnson, use modified viral vectors to deliver viral genes to trigger an immune response.

Inactivated vaccines: Developed by Sinovac and Sinopharm, they are made by using chemical methods to inactivate viruses and provide immune protection.

Recombinant protein vaccines: such as the Novavax vaccine, use fragments of viral proteins to stimulate the immune system.

DNA vaccines: such as India's ZyCoV-D vaccine, which uses a DNA plasmid to encode the viral spike protein.

SARS-CoV inhibitors

Although the spread of the virus has been controlled, the successful development of antiviral drugs against SARS-CoV is necessary for the possible re-emergence of SARS. All proteins and subcellular structures involved in the life cycle of coronaviruses are promising targets for the treatment of diseases caused by coronaviruses. At present, antiviral drug discovery strategies are mainly based on the progress of drug development of different molecular targets, including the following types.

Compounds that block S protein-ACE2-mediated viral entry: SSAA09E2 is a SARS-CoV inhibitor that works by blocking the early interaction between SARS-S and the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2).

Compounds targeting SARS-CoV Mpro: SARS-CoV MPro-IN-2 is a potent SARS-CoV-2 Mpro inhibitor with an IC50 value of 72.07 nM. The main protease of the virus (Mpro), as the main enzyme that deals with viral polyproteins, contributes to the replication and transcription of SARS-CoV-2 in host cells, and is therefore considered an attractive target in drug discovery. SARS-CoV MPro-IN-2 has the potential to study COVID-19.

Compounds targeting papain-like protease (PLPro): Acriflavine hydrochloride is a potent HIF-1 inhibitor with antitumor activity, as well as antimicrobial and antiviral activities. It is a potent papain-like protease (PLpro) inhibitor that can be used to inhibit the activity of SARS-CoV-2.

Compounds targeting SARS-CoV RdRp: RNA-dependent RNA polymerase (RdRp) is an enzyme essential for viral replication that catalyzes viral RNA synthesis through a metal-dependent mechanism. Sofosbuvir and Remdesivir are approved against hepatitis C virus (HCV) and SARS-CoV-2, respectively, demonstrating the effectiveness of targeting RdRp.

Compounds targeting SARS-CoV helicase (non-structural protein 13, NSP13) : SARS-CoV-2-NSP13-in-5 (compound C6) is a potent SARS-CoV-2 nsp13 inhibitor with IC50 values of 50 and 55 μM for ssDNA⁺ ATPase and SSDNA-ATPase, respectively. It can be used to study the effect of anti-COVID-19.

Reference

• Yu, Fei, et al., Receptor-binding domain-specific human neutralizing monoclonal antibodies against SARS-CoV and SARS-CoV-2. Signal Transduction and Targeted Therapy 5.1 (2020): 212.

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