𝐓𝐡𝐞 𝐧𝐨𝐯𝐞𝐥 𝐜𝐨𝐫𝐨𝐧𝐚𝐯𝐢𝐫𝐮𝐬 𝐢𝐬 𝐠𝐞𝐭𝐭𝐢𝐧𝐠 𝐞𝐯𝐞𝐫 𝐦𝐨𝐫𝐞 𝐧𝐨𝐯𝐞𝐥 🦠 TLDR; […]

𝐓𝐡𝐞 𝐧𝐨𝐯𝐞𝐥 𝐜𝐨𝐫𝐨𝐧𝐚𝐯𝐢𝐫𝐮𝐬 𝐢𝐬 𝐠𝐞𝐭𝐭𝐢𝐧𝐠 𝐞𝐯𝐞𝐫 𝐦𝐨𝐫𝐞 𝐧𝐨𝐯𝐞𝐥 🦠

TLDR; SARS-CoV-2 mutates regularly, and we are seeing location-based virus evolution during the lockdown period. A single mutation could impact the universality of any vaccine, antibody therapy or drug targeting the binding domain. It also creates the possibility of repeat infections, like the seasonal flu. Gain-of-function mutations have already occurred (D614G), and the new variants are more virulent (614G becomes the leading strain in any new region into which it is introduced within a matter of weeks) and may mediate repeat infections. Some mutations are in regions that might neutralize antibody binding (V367F). Recombination (S943P) can enable multiple fitness-enhancing mutations to assemble within the same strain making it more pathogenic than the distinct original strains.

Prellis Biologics, Inc pulled together a table of currently known mutations of SARS-CoV-2, and I asked if I could share. Here are some examples from pre-print papers (with attendant caveats):

From BioRxiv, May 2020, https://www.biorxiv.org/content/10.1101/2020.04.29.069054v1
𝙎𝙥𝙞𝙠𝙚 𝙢𝙪𝙩𝙖𝙩𝙞𝙤𝙣 𝙥𝙞𝙥𝙚𝙡𝙞𝙣𝙚 𝙧𝙚𝙫𝙚𝙖𝙡𝙨 𝙩𝙝𝙚 𝙚𝙢𝙚𝙧𝙜𝙚𝙣𝙘𝙚 𝙤𝙛 𝙖 𝙢𝙤𝙧𝙚 𝙩𝙧𝙖𝙣𝙨𝙢𝙞𝙨𝙨𝙞𝙗𝙡𝙚 𝙛𝙤𝙧𝙢 𝙤𝙛 𝙎𝘼𝙍𝙎-𝘾𝙤𝙑-2:

“We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified fourteen mutations in Spike that are accumulating. The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections.

Although the observed diversity among pandemic SARS-CoV-2 sequences is low, its rapid
global spread provides the virus with ample opportunity for natural selection to act upon rare but favorable mutations. This is analogous to the case of influenza. If the pandemic fails to wane, this could exacerbate the potential for antigenic drift and the accumulation of immunologically relevant mutations in the population during the year or more it will take to deliver the first vaccine.

• D614G (a G-to-A base change at position 23,403 in the Wuhan reference strain) is increasing in frequency at an alarming rate, indicating a fitness advantage relative to the original Wuhan strain that enables more rapid spread. We were concerned that if the D614G mutation can increase transmissibility, it might also impact severity of disease. Patients carrying the G614 mutation had higher viral loads… a significant difference was observed.

• S943P (a double base mutation: AGT (S) -> CCT (P)) is located in the fusion core region, and is of particular interest as it is spreading via recombination. Recombination requires simultaneous infection of the same host with different viruses, and the two parental strains have to be distinctive enough to manifest in a detectable way in the recombined sequence. Both criteria were met in Belgium.”

From BioRxiv, April 2020: https://www.biorxiv.org/content/10.1101/2020.03.15.991844v4.full
𝙀𝙢𝙚𝙧𝙜𝙚𝙣𝙘𝙚 𝙤𝙛 𝙍𝘽𝘿 𝙢𝙪𝙩𝙖𝙩𝙞𝙤𝙣𝙨 𝙞𝙣 𝙘𝙞𝙧𝙘𝙪𝙡𝙖𝙩𝙞𝙣𝙜 𝙎𝘼𝙍𝙎-𝘾𝙤𝙑-2 𝙨𝙩𝙧𝙖𝙞𝙣𝙨 𝙚𝙣𝙝𝙖𝙣𝙘𝙞𝙣𝙜 𝙩𝙝𝙚 𝙨𝙩𝙧𝙪𝙘𝙩𝙪𝙧𝙖𝙡 𝙨𝙩𝙖𝙗𝙞𝙡𝙞𝙩𝙮 𝙖𝙣𝙙 𝙝𝙪𝙢𝙖𝙣 𝘼𝘾𝙀2 𝙧𝙚𝙘𝙚𝙥𝙩𝙤𝙧 𝙖𝙛𝙛𝙞𝙣𝙞𝙩𝙮 𝙤𝙛 𝙩𝙝𝙚 𝙨𝙥𝙞𝙠𝙚 𝙥𝙧𝙤𝙩𝙚𝙞𝙣

“Spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the critical determinant of viral tropism and infectivity. Three mutant types displayed higher human ACE2 affinity, and probably higher infectivity, one of which (V367F) was validated by wet bench. The RBD mutation analysis provides insights into SARS-CoV-2 evolution. The emergence of RBD mutations with increased human ACE2 affinity reveals higher risk of severe morbidity and mortality during a sustained COVID-19 pandemic, particularly if no effective precautions are implemented.”

From the Journal of Translational Medicine, April 2020: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02344-6
𝙀𝙢𝙚𝙧𝙜𝙞𝙣𝙜 𝙎𝘼𝙍𝙎-𝘾𝙤𝙑-2 𝙢𝙪𝙩𝙖𝙩𝙞𝙤𝙣 𝙝𝙤𝙩 𝙨𝙥𝙤𝙩𝙨 𝙞𝙣𝙘𝙡𝙪𝙙𝙚 𝙖 𝙣𝙤𝙫𝙚𝙡 𝙍𝙉𝘼-𝙙𝙚𝙥𝙚𝙣𝙙𝙚𝙣𝙩-𝙍𝙉𝘼 𝙥𝙤𝙡𝙮𝙢𝙚𝙧𝙖𝙨𝙚 (𝙍𝙙𝙍𝙥) 𝙫𝙖𝙧𝙞𝙖𝙣𝙩

“SARS-CoV-2 is an RNA coronavirus responsible for the pandemic of COVID-19. RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance.

Methods: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020.

Results: We characterized 8 novel recurrent mutations of SARS-CoV-2. America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp, changing its amino acid composition, emerged on February 20th, 2020 in Italy (Lombardy). The SARS-CoV-2 RdRp (also named nsp12) is a key component of the replication/transcription machinery. RdRps are considered among primary targets for antiviral drug development, against a wide variety of viruses [e.g., Remdesivir]. Naturally occurring mutations can lead to drug resistance phenomena, with a significant loss in the binding affinity of these molecules to the RdRp.

Conclusions: These findings suggest that the virus is evolving, and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. It is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.”