As we look back on the rough year of 2020, with the emergence of a novel coronavirus (COVID-19), we were faced with many uncertainties, with no known standard treatments or available vaccines. Scientists and clinicians work around the clock to understand and combat this virus. So far, tremendous progresses have been made especially in genetically identifying this virus, which in turn leads to rapid development of drugs and vaccines.
With 3 Food and Drug Administration– and 4 China Food and Drug Administration–approved COVID-19 vaccines so far and many more in the pipelines, we are now faced with the dilemma of weighing the effectiveness of these vaccines versus their side effects. The questions that were asked frequently is: should I get vaccinated? In this two-part interview, BIO Integration first interviewed the team of clinicians who were deeply involved in the writing of “The Guidelines for the Diagnosis, Treatment, Prevention and Control of Coronavirus in Adults in China” during the COVID-19 outbreak. This team, led by Professor Shanping Jiang, along with team member Tiantian Tang, now discusses SARS-CoV-2 mutation and progress in vaccine development with BIO Integration.
EE: What is SARS-CoV-2 mutation? How does it mutate? How will the mutation affect the preventive and control measures in this current situation? Will there be another wave of COVID-19 outbreak?
SJ and TT: Virus mutation refers to changes in the genetic materials within the viral genome due to various factors. Similar to other viruses, SARS-CoV-2 can undergo different forms of mutation during the transmission process. The Global Initiative on Sharing Avian Influenza Data database classifies SARS-CoV-2 into several major clades according to its marker mutations, which include clade L (Wuhan variant), clade S (markers C8782T and T28144C), clade V (markers G11083T and G26144T), clade G (markers C241T, C3037T, and A23403G), etc. [1].
Spike protein D614G mutation is typically seen in SARS-CoV-2, in which the virus variant undergoes non-synonymous mutation at nucleotide position 23403 in the genome, resulting in the substitution of aspartic acid (D) with glycine (G) at amino acid position 614 of the virus’s spike protein. At present, this mutant strain has become the dominant variant of SARS-CoV-2 in the global pandemic [2, 3]. Compared with the D614 strain, the G614 variant has stronger infectivity and virus stability, but there is no evidence that the mutation is associated with the severity of the disease. It is also unlikely that the mutation will affect the efficacy of the vaccines [2–4].
Another typical mutation in the spike protein is the N501Y variant, in which asparagine (N) at amino acid position 501 is replaced with tyrosine (Y). The N501Y variant belongs to the B.1.1.7 lineage. In addition to N501Y, this lineage also includes other mutations such as spike protein 69-70del and P681H. Lineage B.1.1.7, also known as SARS-CoV-2 VOC 202012/01 (variant of concern, year 2020, month 12, variant 01), was reported in the UK on December 14, 2020, and is highly infectious [5]. Another variant, 20H/501Y.V2, first appeared in the UK on September 20, 2020, and was subsequently reported in South Africa and other countries. The amino acid position 501 on the spike protein is one of the key sites that directly interact with angiotensin-converting enzyme 2 (ACE2) receptor. Currently, there is no officially published research data to confirm whether the variant has higher transmissibility in the population or whether it is related to the severity of the disease.
The mutation rate of SARS-CoV-2 in the population is calculated to be at around 8×10−4 per site per year [6, 7]. Because of the relatively low evolution rate of SARS-CoV-2 and the highly efficient human-to-human transmission, it was suggested the virus may have already adapted to the human population by the time the large-scale outbreak occurred [4, 8]. The virus mutation has placed a huge pressure upon public pandemic controls. In response, the World Health Organization (WHO) calls on countries and scientists to actively cooperate with the organization, to strengthen the monitoring of virus mutation, to establish an epidemiological model of virus transmission, and to provide the technical support needed in assessing the effect of virus mutation on the risk of reinfection, diagnostics, vaccination, and transmission rate [9].