# Human coronavirus OC43
**Human coronavirus OC43** (HCoV-OC43) is one of four seasonal human coronaviruses that cause the common cold. It is an enveloped, positive-sense single-stranded [RNA virus](https://www.edgepedia.org/rna-virus) of the genus Betacoronavirus, subgenus Embecovirus, species Betacoronavirus 1, and it was first isolated in 1967 from organ cultures of respiratory specimens from patients with cold symptoms.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7098031/) • [2](https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0285481) • [3](https://www.mdpi.com/2076-2607/14/1/43/pdf)
| Key fact | Detail |
|---|---|
| Discovery | Isolated in 1967 from organ culture with serial passage in brains of suckling mice; the "OC" designation refers to organ culture[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7098031/) • [4](https://doi.org/10.5005/jp-journals-10081-1265) |
| Classification | Family Coronaviridae, genus Betacoronavirus, subgenus Embecovirus, species Betacoronavirus 1[2](https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0285481) |
| Receptor | Glycan-based receptors carrying 9-O-acetylated sialic acid, bound by the spike protein[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC7204879/) |
| Clinical role | One of four common HCoVs contributing 15%-30% of common colds in adults; severe lower respiratory infection can occur in infants, elderly, and immunocompromised patients[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC7204879/) |
| Neurotropism | Detected in cerebral neurons from autopsy specimens by immunohistochemistry and in situ hybridization; infects olfactory neurons and spreads by anterograde axonal transport[6](https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2020.584673/full) • [7](https://link.springer.com/article/10.1007/s00401-021-02314-2) |
## Discovery and taxonomy
The first human coronavirus, strain B814, was isolated in 1965 from the nasal discharge of a patient with a common cold. HCoV-OC43 was recovered later, in 1967, using tracheal organ culture and found to be serologically distinct from HCoV-229E, the other prototype human coronavirus isolated in 1966.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC7204879/) The name records its method of growth: strains termed "OC" were grown in organ cultures.[4](https://doi.org/10.5005/jp-journals-10081-1265) One account places the first isolation in Salisbury, England, from patients exhibiting cold symptoms.[3](https://www.mdpi.com/2076-2607/14/1/43/pdf)
Under the ICTV classification, HCoV-OC43 and [HCoV-HKU1](https://www.edgepedia.org/human-coronavirus-hku1) are the two human members of the subgenus Embecovirus within the betacoronaviruses, while HCoV-229E and HCoV-NL63 are alphacoronaviruses.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC7204879/)
## Virion structure and genome
Coronavirus particles are enveloped and about 80-120 nm in diameter, with club-like spike (S) projections. In HCoV-OC43 and HCoV-HKU1, shorter projections of the hemagglutinin-esterase (HE) protein are also observed on the surface. The HE protein binds sialic acids and carries esterase activity that removes acetyl groups from O-acetylated sialic acids, which has been postulated to act as a receptor-destroying enzyme that frees progeny virions from nonpermissive host cells and enhances spreading.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC7204879/)
The genome is a positive-sense single-stranded RNA of more than 30 kb, among the largest of the human coronaviruses, with a 5'-UTR of 210 nucleotides and a 3'-UTR of 288 nucleotides in OC43. The replicase gene occupies the 5' two-thirds of the genome and is processed into 16 non-structural proteins. The 3' third encodes the structural proteins in the order 5'-(HE)-S-E-M-N-3' plus three accessory proteins, ns2a, ns12.9, and protein I, the last encoded internally within the N gene. The ns12.9 protein is a viroporin that facilitates virion morphogenesis and pathogenesis, and the NS2 protein has cyclic phosphodiesterase activity that may modulate cAMP-mediated signaling.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC7204879/)
## Receptor and entry
HCoV-OC43 and HCoV-HKU1 use glycan-based receptors carrying 9-O-acetylated sialic acid, unlike the protein receptors (ACE2, APN, DPP4) used by the other human coronaviruses.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC7204879/) For entry, OC43 employs a caveolin-1-dependent endocytosis pathway, with scission of virus-containing vesicles dependent on dynamin, and IFITM2 or [IFITM3](https://www.edgepedia.org/ifitm3) serve as entry factors that promote its infection.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC7204879/)
## Clinical disease and epidemiology
The four common human coronaviruses generally cause mild upper respiratory tract illness and contribute 15%-30% of common cold cases in human adults, although severe and life-threatening [lower respiratory tract infections](https://www.edgepedia.org/lower-respiratory-tract-infection) can occur in infants, elderly people, or immunocompromised patients.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC7204879/) Early studies reported mainly upper respiratory tract infection for OC43 and related strains, but later work found an 8-19% incidence of lower respiratory tract infection in infants under 18 months of age.[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC7955916/) The clinical features of OC43 infection are symptomatically indistinguishable from other respiratory pathogens such as influenza A viruses and rhinoviruses.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7098031/)
**Seasonality.** The seasonal coronaviruses show annual and seasonal variation.
## Neurotropism
HCoV-OC43 has been detected in cerebral neurons from autopsy specimens using immunohistochemistry and in situ hybridization, and coronavirus has similarly been reported in unspecified cells from multiple sclerosis patients.[6](https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2020.584673/full) Unlike SARS-CoV-2, OC43 readily infects olfactory neurons and moves effectively by anterograde axonal transport to secondary and tertiary olfactory centers in the brain.[7](https://link.springer.com/article/10.1007/s00401-021-02314-2) Continuous propagation in human neural cell cultures produces mutations in the spike glycoprotein, and OC43 can induce persistent infections in human neural cell structures; mechanistically, the genes RIP1 and MLKL appear to play a pivotal role in the neuronal cell death it induces.[9](https://www.mdpi.com/1999-4915/15/2/578) • [3](https://www.mdpi.com/2076-2607/14/1/43/pdf) Human coronavirus infection has also been implicated in chronic conditions including [Parkinson's disease](https://www.edgepedia.org/parkinsons-disease), multiple sclerosis, and peripheral neuropathies, though the evidence remains limited.[6](https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2020.584673/full)
## Origin and the Russian flu hypothesis
HCoV-OC43 and bovine coronavirus (BCoV) show remarkable antigenic and genetic similarity. This timing has led to the proposal, known as the Russian influenza-coronavirus theory, that OC43 emerged from cattle and caused the 1889-1890 "Russian flu" pandemic rather than an influenza virus.
## Evolution after 2020
Bayesian analysis of longitudinal surveillance data found accelerated genomic evolution of HCoV-OC43 following the COVID-19 pandemic: the spike gene substitution rate of the currently dominant genotype K increased 3.76-fold post-2020, to 8.9403 × 10-4 nucleotide substitutions per site per year (95% HPD: 4.9075 × 10-4 to 1.3053 × 10-3).[10](https://pmc.ncbi.nlm.nih.gov/articles/PMC12994797/) A 10-year study of the S gene in Barcelona (2014-2024) found continuous circulation with a high level of genetic diversity, and surveillance in Riyadh during winter 2025-2026 detected OC43 in 26 of 293 coronavirus-positive cases (8.87%), with persistent genotype C and conserved N-glycosylation motifs.[11](https://www.sciencedirect.com/science/article/pii/S0213005X26001898) • [12](https://www.mdpi.com/1422-0067/27/8/3418)
## References
1. [Zoonotic origins of human coronaviruses, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7098031/)
2. [Candidate historical events for the emergence of Human Coronavirus OC43: A critical reassessment of the molecular evidence, PLOS One](https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0285481)
3. [Type of the Paper (Article), Microorganisms (MDPI)](https://www.mdpi.com/2076-2607/14/1/43/pdf)
4. [Coronavirus Disease-2019 and More: The Story of Coronaviruses So Far](https://doi.org/10.5005/jp-journals-10081-1265)
5. [Human Coronavirus-229E, -OC43, -NL63, and -HKU1 (Coronaviridae), Encyclopedia of Virology, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7204879/)
6. [Coronavirus Infection of the Central Nervous System: Animal Models in the Time of COVID-19, Frontiers in Veterinary Science](https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2020.584673/full)
7. [The olfactory nerve is not a likely route to brain infection in COVID-19, Acta Neuropathologica](https://link.springer.com/article/10.1007/s00401-021-02314-2)
8. [Emergent human coronaviruses – History informs the future, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7955916/)
9. [Human Coronavirus OC43 as a Low-Risk Model to Study COVID-19, Viruses (MDPI)](https://www.mdpi.com/1999-4915/15/2/578)
10. [Pandemic-driven immune imprinting accelerates evolution of human coronavirus OC43, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC12994797/)
11. [Spike gene evolution in HCoV-OC43: Evidence of post-pandemic selective expansion, ScienceDirect](https://www.sciencedirect.com/science/article/pii/S0213005X26001898)
12. [Molecular Surveillance of Coronaviruses in Riyadh (2025-2026), IJMS (MDPI)](https://www.mdpi.com/1422-0067/27/8/3418)
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*Topic: Encyclopedia › Life and health › Microorganisms and fungi › Viruses and acellular agents › Viruses of animals and humans › Coronaviruses › Embecoviruses (betacoronavirus lineage A)*
*Initially written Sep 17, 2026 · Reviewed: Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license