Mutation "hotspots" of SARS-CoV-2

The type and number of mutations can differ based on region. SARS-CoV-2 in Europe and North America were found to have higher rates and variety of mutations compared to regions closer to the origin of the virus like Asia. Differences in mutations per region increased overtime outside of Asia. 

Mutations of SARS-CoV-2 can differ by Region

Evolution of SARS-CoV-2 by Origin

Through careful examination of viral structural/non-structural proteins as well as infection mechanism, the 2003 SARS-CoV and the current 2019nCoV are thought to be very similar in phylogenic. Based on complete sequencing, the current 2019-nCoV is evolutionary related to SARS-CoV long range-conserved amino acid sequences with a few variations in the accessory proteins and base substitutions in non-structural proteins (Wu et al., 2020). Even before 2003, many different coronaviruses have similar conserved proteins and replication pathway all leading to annually 15-30% of respiratory infections in humans. Individuals of older age, with pre-existing illnesses, or with compromised immunity are the most susceptible to infections and often associated with the highest mortality. 
Currently, the 2019-nCoV has been reported to have the highest pathenogenicity and fatality out of all coronaviruses. This can be explained based on differences in tolerance to genetic variability. For instance, both the 2003 SARS-CoV and current 2019-nCoV are very tolerant to genetic variations. Both strains of coronaviruses have shown their potential to pass through species barrier from bats, pangolins, mice, and bovine all the way to mammals including humans (Guan et al., 2003). In other words, higher tolerance to genetic variability could imply greater chances of horizontal gene transfer across species. Looking back to 2003, the same characteristics can be seen in SARS-CoV, where it was hypothesized to be found first in Chinese horseshoe bats in Guangdong Province.

Phylogeny and Tropism

An analysis of 86 complete or near-complete SARS-CoV-2 genomes acquired from GISAID was done to examine mutations in the SARS-CoV-2 genome. The samples of SARS-CoV-2 were taken from patients in China, the USA, Australia, Japan, France, Singapore, England, Taiwan, South Korea, Belgium, Germany, and Vietnam.

Genetic diversity and evolution of SARS-CoV-2

- COVID-19 Virology in Comparison to SARS-CoV and MERS
- Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis

Comparison of SARS-CoV-2 genomes to other related genomes

- Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study

Deletions in the SARS-CoV-2 Genome

Researchers at the University of Bologna conducted the largest genomic study of SARS-CoV-2 to date, analyzing 48,635 different genomes and their mutations. There are currently six known strains around the world with differential geographic and genomic distribution, though there is little genetic variability between them, which is beneficial because a viable vaccine would likely be effective in fighting all of them.


The Six Strains of COVID-19

As of mid-December 2020, a new strain of SARS-CoV-2, the virus that causes COVID-19, was discovered in the United Kingdom. According to recent studies, this new strain can be up to 70% more transmissible.

UK Variant of SARS-CoV-2

A new strain of the SARS-CoV-2 virus was discovered in the Eastern Cape of South Africa as of the end of 2020. This new strain is called 501Y.V2.

South African Variant of SARS-CoV-2

Investigations are still ongoing in determining the current evolution and mutating nature of SARS-CoV-2, which will aid scientists in understanding more about this virus and in developing effective treatments and vaccines against the disease. 

University of Michigan - Ann Arbor

- Animal Studies on SARS-CoV-2 Virology
- Antigen Detection
- Classification
- Evolution and Mutations
- Methods of Host Cell Infection and Exploitation
- Stability in different environmental conditions
- Structure
- Vaccine Candidates, Immunogenicity, and Adaptive Immunity
- Reinfection

Focuses of Virology of COVID-19

SARS-CoV-2 is comprised of four main structural components: the spike glycoprotein (S), the small envelope glycoprotein (E), the membrane glycoprotein (M), and the nucleocapsid protein (N). There are also several accesory proteins. 

Structure of SARS-CoV-2

- Manipulation of Innate Immune and Pro-inflammatory Response

Methods of Host Cell Infection and Exploitation

A study found that SARS-CoV-2 can be highly sensitive to heat. The virus was still detectable after being left out for 14 days in a 4°C room, while the virus inactive 5 minutes after being left in a 70°C. The study also found a difference in stability on different surfaces, such as paper, plastic, and metal.  At room temperature, the virus is highly stable in a range of pH3 - pH10. However, the standard disinfectant method was still able to affect the virus, with the researchers finding no active infection in different disinfectants after an incubation of 5 minutes (except for hand soap).

Stability of SARS-CoV-2 in different environmental conditions

Evolution and Mutations of SARS-CoV-2

- Application of Rhesus Macaques for Studying SARS-CoV-2 Virology
- Application of Syrian Hamsters for Studying SARS-CoV-2 Virology
- Application of Mosquitoes for Studying SARS-CoV-2 Virology
- Application of African Green Monkeys for Studying SARS-CoV-2 Virology

Animal Studies on SARS-CoV-2 Virology

So far, vaccines consist of either inactivated or weakened versions of antigens or virions. Many pharmaceutical companies like Pfizer and Moderna are developing inactivated antigens in the form of mRNA, DNA, and proteins from the viral envelope or capsid that are often fragmented. 

Vaccine Candidates, Immunogenicity, and Adaptive Immunity

Until vaccine has passed all preclinical and clinical trials as well as FDA approval, the best approach to containing the pathogenicity and infectivity of COVID-19 will involve testing. The Safra center at Harvard advised to have up to 5 million tests being conducted within a day. Testing will not only slow down the spread, but also allow reopening of businesses and schools. So far, many testing methods involve viral RNAs or antigens. For detecting viral RNAs, most involve using RT-qPCR conjugated with Next Generation Sequencing to identify specific unique viral sequences. Recently, SHERLOCK detection technique utilizing CRISPR-Cas13 was tested in Broad Institute using a catalytically dead Cas13 to bind to specific viral sequences. On the other hand, detection of viral antigens involve either using ELISA with selected antibodies against viral antigens or using lateral flow assay.

Antigen Detection

Until August 28, 2020, there has been several cases of reinfections around the world (Hong Kong, Belgium, the Netherlands, and the US). 

Reinfection of SARS-CoV-2

The coronaviruses belong to the broad viral order Nidovirales within the family, Coronaviridae, notoriously known to be infecting mammals and humans in the recent years. In general, they can be commonly distinguished by their unique morphological structures of spherical or disk-like envelopes embedded with glycoproteins (Burrell et al., 2017). In terms of its genetic composition, it has a large positive sense RNA (33.5 kb) belonging to Group VI in the Baltimore classification. Other shared similarities include highly conserved genomes, Replicase gene upstream of structural and accessory genes as well as the translation of many nonstructural mRNAs from ribosomal frameshift. These viruses are very diverse and can be further subdivided into 4 subfamilies: alpha-, beta-, delta-, and gamma-coronaviruses based on serology (Fehr et al., 2015). 

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