This new peer-reviewed publication describes viruses isolated from patient samples from the first and second wave of COVID-19 in Houston, Texas last spring.
Of note the authors analyzed the nsp12 polymerase gene that encodes for an RNA-dependent RNA polymerase (RdRp; also referred to as Nsp12) used in viral replication. As Remdesivir, the adenosine analog used as a COVID-19 therapy, is inserted into the RNA chain by this RNA polymerase conferring inhibition of viral replication, it is important to ascertain the prevalence of variations in RdRp.
Additionally the authors reveal the mutational analysis of the SARS-CoV-2 spike protein including the dominant aspartic acid to glycine amino acid mutation at the 614 position (D614G) depicted in Figure 6 below. The researchers show this single amino acid substitution confers a higher viral load in patient samples which likely results in higher transmission and infectivity.
A link to the full research article is available here.
KEY FIGURES:
Figure 1:
(A) Confirmed COVID-19 cases in the Greater Houston Metropolitan region. Data represent cumulative number of COVID-19 patients over time through 7 July 2020. Counties include Austin, Brazoria, Chambers, Fort Bend, Galveston, Harris, Liberty, Montgomery, and Waller. The shaded area represents the time period (indicated as month/day along the x axis) during which virus genomes characterized in this study were recovered from COVID-19 patients. The red line represents the number of COVID-19 patients diagnosed in the Houston Methodist Hospital Molecular Diagnostic Laboratory. (B) Distribution of strains with either the Asp614 or Gly614 amino acid variant in spike protein among the two waves of COVID-19 patients diagnosed in the Houston Methodist Hospital Molecular Diagnostic Laboratory. The large inset shows major clade frequency for the time frame studied (indicated as month-day to month-day along the x axis).
ABSTRACT:
We sequenced the genomes of 5,085 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains causing two coronavirus disease 2019 (COVID-19) disease waves in metropolitan Houston, TX, an ethnically diverse region with 7 million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston and from viruses recovered in an ongoing massive second wave of infections. The virus was originally introduced into Houston many times independently. Virtually all strains in the second wave have a Gly614 amino acid replacement in the spike protein, a polymorphism that has been linked to increased transmission and infectivity. Patients infected with the Gly614 variant strains had significantly higher virus loads in the nasopharynx on initial diagnosis. We found little evidence of a significant relationship between virus genotype and altered virulence, stressing the linkage between disease severity, underlying medical conditions, and host genetics. Some regions of the spike protein—the primary target of global vaccine efforts—are replete with amino acid replacements, perhaps indicating the action of selection. We exploited the genomic data to generate defined single amino acid replacements in the receptor binding domain of spike protein that, importantly, produced decreased recognition by the neutralizing monoclonal antibody CR3022. Our report represents the first analysis of the molecular architecture of SARS-CoV-2 in two infection waves in a major metropolitan region. The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution.
IMPORTANCE:
There is concern about second and subsequent waves of COVID-19 caused by the SARS-CoV-2 coronavirus occurring in communities globally that had an initial disease wave. Metropolitan Houston, TX, with a population of 7 million, is experiencing a massive second disease wave that began in late May 2020. To understand SARS-CoV-2 molecular population genomic architecture and evolution and the relationship between virus genotypes and patient features, we sequenced the genomes of 5,085 SARS-CoV-2 strains from these two waves. Our report provides the first molecular characterization of SARS-CoV-2 strains causing two distinct COVID-19 disease waves.
Figure 6:
Location of amino acid substitutions mapped on the SARS-CoV-2 spike protein. The figure presents a model of the SARS-CoV-2 spike protein with one protomer shown as ribbons and the other two protomers shown as a molecular surface. The Cα atom of residues found to be substituted in one or more virus isolates identified in this study is shown as a sphere on the ribbon representation. Residues found to be substituted in 1 to 9 isolates are colored tan, those substituted in 10 to 99 isolates yellow, those substituted in 100 to 999 isolates red (H49Y and F1052L), and those substituted in >1,000 isolates purple (D614G). The surface of the amino-terminal domain (NTD) that is distal to the trimeric axis has a high density of substituted residues. RBD, receptor binding domain.
DOI: 10.1128/mBio.02707-20