Comparison of peptides derived from human cardiac proteins and SARS/CoV-2 proteins

The rapid spread of severe acute respir syndrome coronavirus 2 virus (SARS-CoV-2) is what has led to the coronavirus infection in 2019 (COVID-19). Cardiac injuries are a frequent complication associated with COVID-19. The molecular foundation of this phenotype remains unclear.

Study: Genetic alteration of human MYH6 is mimicked by SARS-CoV-2 polyprotein and mapping of viral variants of cardiac interest. Image Credit: Kateryna Kon/Shutterstock

Scientists believe that molecular mimicry could play a crucial role in the autoimmune inflammatory response that is seen in COVID-19 patients. A new study was published on the preprint server. It examined whether linear peptides in proteins (primarily expressed in heart) also exist in the SARS-2 proteome.

Cardiac injury, COVID-19

Numerous studies have documented the prevalence of cardiac injuries that are a result of COVID-19. Myocarditis was reported in a few instances after receiving the mRNA COVID-19 vaccination. The mechanisms that cause myocardial inflammation after COVID-19 vaccination and infected remain a mystery. One hypothesis is that T lymphocytes or antibodies that recognize SARS-CoV-2 Antigens and mediate virus neutralization could react with host proteins to trigger an immune response.

The development of large-scale multi-omic datasets is possible due to advances in sequencing technology. These new resources have revealed the transcriptional signatures of a variety of healthy human cells and tissues. Over 200 countries have contributed more than 4.85 million SARS-CoV-2 genomes into the GISAID database. These large-scale data sets have allowed researchers to study the molecular mimicry potential between human cardiac proteins (SARS-CoV-2) and other large-scale data sets.

Key findings

Scientists have compared the library comprising 8-mer peptides that comprise 136,704 of human proteins with 9,926 8-mers from all 17 viral proteins in the SARS-CoV-2 proteome reference. The human proteins also included splicing variants. The analysis revealed that no 8-mers were the same between the SARS-CoV-2 proteome and the reference proteome of humans. It was interesting to observe that 45 8-mers differed by only one amino acid.

Protein-coding mutations from 141,456 individuals were analyzed. The results showed that one of the 8-mers in the SARS-CoV-2 replicase polyprotein 1a/1ab (KIALKGGK) was exactly similar to an MYH6 peptide encoded in the c.5410C>A (Q1804K) genetic variation. This genetic variation is rare in a number of sub-groups. This genetic variation is present in 0.08% of Africans/African Americans and 0.3 percent of East Asians. It also affects 0.06% of South Asians as well as 0.003% Latinos/Admixed Americans.

Scientists have further analyzed 4.85 million SARS-CoV-2 genomes spanning over 200 countries, and discovered that the evolution of the virus has led to 20 more 8-mer peptides. These peptides are identical to human heart-enriching proteins encoded in reference sequences or genetic variants. Future research will need to reveal if such mimicry causes cardiac inflammation during or after COVID-19 illness.

Scientists have recommended a more thorough investigation of variants of SARS-CoV-2 that contain similar peptides to human cardiac proteins as “viral variants of interest to the cardiac system’. The possibility of a molecular mimicry between the antigen encoded in mRNA vaccines and human cardiac proteins ought to also be studied, given the prevalence of myocarditis among certain individuals following the administration of COVID-19 mRNA-based vaccine.


First, the human proteins that were analyzed were selected by their expression levels in the heart tissue. Mimicked proteins could be found in cardiac tissues as well as other tissues, but they were not accounted for in the present study. Secondly different mechanisms (e.g. epitope spread, bystander activation and persistence of the virus) could trigger the development of an immune system after infection with a virus. It could also be a matter of pure chance that identical peptides are present in cardiac proteins and the SARS-CoV-2 proteome. It is possible that peptides of less similarity may contribute to immunologic mimicry.


By analyzing the overlap between human genetic variation in cardiac proteins and SARS-CoV-2’s evolution, scientists have identified potential molecular mimicry candidates. These candidates have the potential to trigger inflammation of the cardiac system in COVID-19 patients. Follow-up functional studies to assess the capacity of SARS-CoV-2 T cells and antibodies to cross-react with these peptides will be essential. Researchers have also highlighted that this method could be generalized to identify and categorize potential mimicry candidates from a wide variety of human tissues affected by other autoimmune responses in patients suffering from COVID-19.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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Gemma Wilson

Gemma is a journalism graduate with keen interest in covering business news – specifically startups. She has as a keen eye for technologies and has predicted quite a few successful startups over the last couple of years.

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