SARS-CoV-2 Mutations and their Viral Variants

Abstract

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occur spontaneously during replication. Thousands of mutations have accumulated and continue to since the emergence of the virus. As novel mutations continue appearing at the scene, naturally, new variants are increasingly observed. Since the first occurrence of the SARS-CoV-2 infection, a wide variety of drug compounds affecting the binding sites of the virus have begun to be studied. As the drug and vaccine trials are continuing, it is of utmost importance to take into consideration the SARS-CoV-2 mutations and their respective frequencies since these data could lead the way to multi-drug combinations. The lack of effective therapeutic and preventive strategies against human coronaviruses (hCoVs) necessitates research that is of interest to the clinical applications. The reason why the mutations in glycoprotein S lead to vaccine escape is related to the location of the mutation and the affinity of the protein. At the same time, it can be said that variations should occur in areas such as the receptor-binding domain (RBD), and vaccines and antiviral drugs should be formulated by targeting more than one viral protein. In this review, a literature survey in the scope of the increasing SARS-CoV-2 mutations and the viral variations is conducted. In the light of current knowledge, the various disguises of the mutant SARS-CoV-2 forms and their apparent differences from the original strain are examined as they could possibly aid in finding the most appropriate therapeutic approaches.

Keywords: COVID-19; Mutation; Receptor-binding domain; SARS-CoV-2; Spike protein; Viral variants.

Fig. 1

The to-date defined surface protein structure of of SARS-CoV-2 (+ssRNA: single-stranded positive-sense RNA).

Fig. 2

Cell entry of SARS-CoV-2, replication cycle and synthesis of viral components. 1: SARS-CoV-2 binds via the S glycoprotein to the ACE-2 receptor expressed in the host cell. 2. SARS-CoV-2 enters the cell with clathrin-coated pits. 3. The clathrin structures are separated from the main structure. 4. Endosome fusion (with dynein) takes place to release the viral RNA genome. 5. The dynein units are separated from the structure and the endosome begins to open. 6. The opening of the endosome and release of the viral RNA genome. The viral RNA genome is synthesized using host ribosomes, viral polymerase. 7. Genomic and subgenomic RNA synthesis takes place in the synthesis of viral proteins. Then, with the help of ribosomes, viral RNAs are transmitted and viral proteins are synthesized. 8. Viral components come together to form the endosomal structure, then to make up for SARS-CoV-2.

Fig. 3

The structure of the SARS-CoV-2 spike (S) protein. (RBD: receptor binding domain; NDT: N-terminal domain; FP: fusion protein; T.A.: transmembrane anchor and I.T.: intracelluar tail).

Fig. 4

Countries with the fastest-spreading variants. B.1.1.7: Denmark, United States of America, France, Spain, Belgium, Netherlands, Italy, Switzerland, Ireland, Turkey, Israel, Portugal, Austria, Sweden, Australia, Finland, Germany, Norway, Nigeria, Slovakia, Ghana, India, Singapore, New Zealand, Jordan, Canada, Romania, Luxembourg, South Korea, Brazil, United Arab Emirates, Iceland, Poland, Czech Republic, Sri Lanka, Northern Macedonia, Saint Lucia, Aruba, Hong Kong, Thailand, Montenegro, Mexico, Ecuador, Bosnia and Herzegovina, Hungary, Latvia, Slovenia, Greece, Guadeloupe, Jamaica, Barbados, Kosovo, Bangladesh, Gambia, Cayman Islands, Republic of Serbia, Malaysia, Democratic Republic of the Congo, Taiwan, Pakistan, Peru, Iran, Argentina, Mayotte, Curaçao, Oman, Senegal, Kuwait, Dominican Republic, Trinidad and Tobago, South Africa, B.1.351: Mayotte, United Kingdom, Belgium, France, Netherlands, Switzerland, Mozambique, Botswana, Zambia, New Zealand, Australia, Austria, Denmark, United States of America, Turkey, Germany, Ireland, Israel, Kenya, Finland, Sweden, United Arab Emirates, Ghana, South Korea, Thailand, Spain, Canada, Portugal, Luxembourg, Singapore, Democratic Republic of the Congo, Italy, Norway, Panama, Bangladesh, P.1: Brazil, Switzerland, Colombia, Italy, Belgium, Japan, France, United States of America, Netherlands, French Guiana, Spain, South Korea, Mexico, Faroe Islands, Peru, B.1.525: Denmark, United Kingdom, Nigeria, United States of America, France, Canada, Ghana, Australia, Netherlands, Jordan, Singapore, Finland, Mayotte, Belgium, Spain. More than one mutant type is seen at once in the blackened countries or regions.