An update on COVID-19: SARS-CoV-2 variants, antiviral drugs, and vaccines

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious and pathogenic virus that first appeared in late December 2019. This SARS-CoV-2 causes an infection of an acute respiratory disease called "coronavirus infectious disease-2019 (COVID-19). The World Health Organization (WHO) declared this SARS-CoV-2 outbreak a great pandemic on March 11, 2020. As of January 31, 2023, SARS-CoV-2 recorded more than 67 million cases and over 6 million deaths. Recently, novel mutated variants of SARS-CoV are also creating a serious health concern worldwide, and the future novel variant is still mysterious. As infection cases of SARS-CoV-2 are increasing daily, scientists are trying to combat the disease using numerous antiviral drugs and vaccines against SARS-CoV-2. To our knowledge, this is the first comprehensive review that summarized the dynamic nature of SARS-CoV-2 transmission, SARS-CoV-2 variants (a variant of concern and variant of interest), antiviral drugs and vaccines utilized against SARS-CoV-2 at a glance. Hopefully, this review will enable the researcher to gain knowledge on SARS-CoV-2 variants and vaccines, which will also pave the way to identify efficient novel vaccines against forthcoming SARS-CoV-2 strains.

Keywords: ACE2, Angiotensin-converting enzyme 2; Antiviral drugs; COVID-19; COVID-19, Coronavirus infectious disease-2019; EUA, Emergency Use Authorization; FDA, Food and Drug Administration; NIH, National Institutes of Health; RBD, Receptor-binding domain; SARS-CoV-2; SARS-CoV-2 variants; SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2; VOC, Variants of Concern; VOI, Variants of Interests; Vaccines; WHO, World Health Organization.

Fig. 1

Structure of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Fig. 2

Routes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) entry: The SARS-CoV-2 enters target cells either by (A) membrane fusion or by (B) receptor-mediated endocytosis. (A) In membrane fusion, the S protein is mediated by transmembrane peptidase/serine subfamily member 2 (TMPRSS2), resulting in fusion of the viral membrane with the plasma membrane. (B) Binding of SARS-CoV-2 to ACE2 receptor leads to virus uptake into endosomes. The spike (S) glycoprotein is activated by cysteine peptidase cathepsin L in endo-lysosomes. In both way (A or B), the RNA genetic material of the virus will enter and starts RNA replication. (B) Binding of SARS-CoV-2 to ACE2 receptor leads to virus uptake into endocytosis. The spike (S) glycoprotein is activated by cysteine peptidase cathepsin L in endo-lysosomes. In both way (A or B), the RNA genetic material of the virus will enter and starts RNA replication.

Fig. 3

Entry mechanism of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and target drugs against SARS-CoV-2: The SARS-CoV-2 enters through major routes; When angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) co-expressed on the host cell surface, SARS-CoV-2 binds to the ACE2 and get activated by TMPRSS2 via proteolytic cleavage to mediate virus-cell fusion (which can be inhibited by monoclonal antibodies, spike (S) binding protein, and small molecules). Step 1-The SARS-CoV-2 enters the host cell receptor via its spike (S) protein. After receptor binding, the SARS-CoV-2 enters the cytosol with the help of the S protein (which can be blocked by Hydroxychloroquine and Baricitinib). Once the viral genome enters the cytoplasm (Step 2) (which can be blocked by Molnupiravir), translation of the viral genome (Steps 3 & 4) occurs and forms a viral replication-transcription complex (Step 5) directly from sub-genomic RNA (+sense) (which can be blocked by Ribavirin, Remdesivir, and Favipiravir). This viral replication-transcription complex contains Envelope (E), S, and Membrane (M) proteins (which can be blocked by Oseltamivir, Ribavirin, and Favipiravir) that will translate from the RNA (Step 6) and will enter the endoplasmic reticulum (Step 6) and move to the endoplasmic reticulum-golgi intermediate compartment (ERGIC) (which can be blocked by Lepinavir) (Step 7). The viral replication-transcription complex contains nucleocapsid (proteins that interact with M proteins in the ERGIC and form a mature virion (Step 8). This mature virion will move outside the cell via the exocytic pathway (Step 9).

Fig. 4

Different types of vaccines used for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A) mRNA vaccine works by using a piece of mRNA that corresponds to a viral protein. After receiving the mRNA vaccination, human cells will produce a foreign viral protein. As part of the normal immune system, the immune system of the body will be able to recognize the foreign viral protein and will start to produce antibodies against the foreign viral protein. These antibodies will protect humans against SARS-CoV-2 infection. B) In the DNA vaccine, genetic material from the SARS-CoV-2 is placed in an altered form (viral vector). When this viral vector is injected into cells, it will deliver the genetic material of SARS-CoV-2 and will start to produce a foreign viral protein. The normal immune system of the body will recognize the foreign viral protein and will start produce antibodies against the foreign viral protein. These antibodies will protect humans against SARS-CoV-2 infection. C) Protein subunit vaccine. This vaccine includes only slices of a virus, which stimulates the immune response. This vaccine contains harmless S protein and once our body recognizes the S proteins, it will create antibodies and defensive white blood cells. If humans infected with SARS-CoV-2, these antibodies would fight against the SARS-CoV-2.