Editing Rhinovirus

{{Short description|Genus of viruses (Enterovirus)}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Paraphyletic group
| image = Rhinovirus isosurface.png
| image_alt = Isosurface of a human rhinovirus, showing protein spikes
| image_caption = Rhinovirus
| auto = virus
| parent = Enterovirus
| includes =
* ''Rhinovirus A''
* ''Rhinovirus B''
* ''Rhinovirus C''
| excludes =
* ''Enterovirus A''
* ''Enterovirus B''
* ''[[Enterovirus C]]''
* ''[[Enterovirus D]]''
* ''[[Enterovirus E]]''
* ''Enterovirus F''
* ''Enterovirus G''
* ''Enterovirus H''
* ''Enterovirus I''
* ''Enterovirus J''
* ''Enterovirus K''
* ''Enterovirus L''
}}

The '''rhinovirus''' (from the {{langx|grc|ῥίς|rhis}} "nose", {{smallcaps|[[Genitive case|gen]]}} {{lang|grc|ῥινός}}, <small>romanized:</small> {{transliteration|grc|rhinos}} "of the nose", and the {{langx|la|[[Virus#Etymology|vīrus]]}}) is a [[Positive-sense single stranded RNA virus|positive-sense, single-stranded RNA virus]] belonging to the [[genus]] ''[[Enterovirus]]'' in the family ''[[Picornaviridae]]''. Rhinovirus is the most common viral infectious agent in humans and is the predominant cause of the [[common cold]].<ref name="health.hawaii.gov">{{Cite web |title=Rhinovirus (Common Cold) {{!}} Disease Outbreak Control Division |url=https://health.hawaii.gov/docd/disease_listing/rhinovirus/#:~:text=About%20This%20Disease,children%20may%20have%20even%20more. |access-date=2024-11-20 |website=health.hawaii.gov}}</ref>

The three species of rhinovirus (A, B, and C) include at least 165 recognized types that differ according to their surface [[antigens]] or [[genetics]].<ref name="ictv.global">{{Cite web |title=Genus: Enterovirus {{!}} ICTV |url=https://ictv.global/report/chapter/picornaviridae/picornaviridae/enterovirus |access-date=2023-12-29 |website=ictv.global}}</ref> They are among the smallest viruses, with diameters of about 30 nanometers. By comparison, other viruses, such as [[smallpox]] and [[vaccinia]], are around ten times larger at about 300 [[nanometer]]s, while [[Orthomyxoviridae|influenza viruses]] are around 80–120&nbsp;nm.

Rhinoviruses are transmitted through [[aerosol]]s, respiratory droplets, [[fomite]]s, and direct person-to-person contact.<ref name="Wang_2021" /> They primarily infect nasal [[epithelial cells]] in the airway and cause mild symptoms such as sore throat, cough, and nasal congestion.<ref name="Jacobs Lamson et al 2013">{{cite journal |vauthors=Jacobs SE, Lamson DM, St George K, Walsh TJ |date=January 2013 |title=Human rhinoviruses |journal=Clinical Microbiology Reviews |volume=26 |issue=1 |pages=135–162 |doi=10.1128/CMR.00077-12 |pmc=3553670 |pmid=23297263}}</ref><ref name="www.cdc.gov_2023">{{Cite web |date=2023-03-09 |title=Rhinoviruses: Common Colds {{!}} CDC |url=https://www.cdc.gov/ncird/rhinoviruses-common-cold.html |access-date=2023-12-28 |website=www.cdc.gov |language=en-us}}</ref> However, rhinovirus infection can cause more severe disease in infants,<ref>{{cite journal |last1=van Benten |first1=I |last2=Koopman |first2=L |last3=Niesters |first3=B |last4=Hop |first4=W |last5=van Middelkoop |first5=B |last6=de Waal |first6=L |last7=van Drunen |first7=K |last8=Osterhaus |first8=A |last9=Neijens |first9=H |last10=Fokkens |first10=W |title=Predominance of rhinovirus in the nose of symptomatic and asymptomatic infants |journal=Pediatric Allergy and Immunology |date=2003 |volume=14 |issue=5 |pages=363–370 |doi=10.1034/j.1399-3038.2003.00064.x |pmid=14641606|pmc=7168036 }}</ref><ref>{{cite journal |last1=Auvray |first1=C |last2=Perez-Martin |first2=S |last3=Schuffenecker |first3=I |last4=Pitoiset |first4=C |last5=Tarris |first5=G |last6=Ambert-Balay |first6=K |last7=Martin |first7=L |last8=Dullier-Taillefumier |first8=N |last9=Bour |first9=JB |last10=Manoha |first10=C |title=Sudden Infant Death Associated with Rhinovirus Infection |journal=Viruses |date=2024 |volume=16 |issue=4 |page=518 |doi=10.3390/v16040518 |doi-access=free |pmid=38675861|pmc=11054477 }}</ref> the elderly, and the [[immunocompromised]]. Rhinoviruses are also recognized as a major cause of [[asthma]] exacerbations.<ref>{{cite journal | vauthors = Friedlander SL, Busse WW | title = The role of rhinovirus in asthma exacerbations | journal = The Journal of Allergy and Clinical Immunology | volume = 116 | issue = 2 | pages = 267–273 | date = August 2005 | pmid = 16083778 | doi = 10.1016/j.jaci.2005.06.003 }}</ref>

As of April 2024, there are no [[FDA]]-approved [[vaccines]] or antiviral treatments for rhinovirus infection.<ref name="www.cdc.gov_2023" />

== History == 
In 1953, when a cluster of nurses developed a mild respiratory illness, [[Winston Price]], from [[Johns Hopkins University]], took nasal passage samples and isolated the first rhinovirus, which he called the JH virus, named after [[Johns Hopkins]].<ref name=Offit2007>{{cite book | vauthors = Offit PA |author-link=Paul Offit |title=Vaccinated: One Man's Quest to Defeat the World's Deadliest Diseases |date=2007 |publisher=HarperCollins |isbn=978-0-06-122795-0 |pages=66–68 }}</ref><ref name="PHR1959">{{cite book|title=Public Health Reports|url=https://books.google.com/books?id=XFZ6ZQDXb0QC&pg=PA9 |volume=74 |year=1959 |publisher=The Service|page=9}}</ref> His findings were published in 1956.<ref name=Kennedy>{{cite journal | vauthors = Kennedy JL, Turner RB, Braciale T, Heymann PW, Borish L | title = Pathogenesis of rhinovirus infection | journal = Current Opinion in Virology | volume = 2 | issue = 3 | pages = 287–293 | date = June 2012 | pmid = 22542099 | pmc = 3378761 | doi = 10.1016/j.coviro.2012.03.008 }}</ref>

In 2006, advancements in molecular testing techniques for identifying rhinoviruses in clinical specimens led to the discovery of rhinovirus C species in samples from Queensland, Australia and New York City, United States. The [[International Committee on Taxonomy of Viruses|ICTV]] formally designated RV-C as a separate species in 2009.<ref name="Jacobs Lamson et al 2013" />

== Transmission ==
Rhinoviruses may be spread via airborne [[aerosols]], [[respiratory droplet]]s and from [[fomite]]s (contaminated surfaces), including direct person-to-person contact.<ref name="Wang_2021">{{cite journal | vauthors = Wang CC, Prather KA, Sznitman J, Jimenez JL, Lakdawala SS, Tufekci Z, Marr LC | title = Airborne transmission of respiratory viruses | journal = Science | volume = 373 | issue = 6558 | pages = eabd9149 | date = August 2021 | pmid = 34446582 | pmc = 8721651 | doi = 10.1126/science.abd9149 }}</ref> Rhinoviruses can survive on surfaces such as stainless steel or plastic for several hours. 
[[Airborne transmission| Airborne precautions]]<ref name="andrup_krogfelt_hansen_madsen_1">{{cite journal | vauthors = Andrup L, Krogfelt KA, Hansen KS, Madsen AM | title = Transmission route of rhinovirus - the causative agent for common cold. A systematic review | journal = American Journal of Infection Control | volume = 51 | issue = 8 | pages = 938–957 | date = August 2023 | pmid = 36535318 | doi = 10.1016/j.ajic.2022.12.005 }}</ref> are likely effective in reducing transmission, while other precautions such as hand-washing or cleaning surfaces with disinfectants are known effective in preventing rhinovirus transmission.<ref>{{cite journal | vauthors = Kutter JS, Spronken MI, Fraaij PL, Fouchier RA, Herfst S | title = Transmission routes of respiratory viruses among humans | journal = Current Opinion in Virology | volume = 28 | pages = 142–151 | date = February 2018 | pmid = 29452994 | pmc = 7102683 | doi = 10.1016/j.coviro.2018.01.001 | series = Emerging viruses: intraspecies transmission • Viral Immunology }}</ref>

== Signs and symptoms ==
{{Main|Common cold}}Rhinoviruses are the primary cause of the [[common cold]]. [[Symptom]]s include [[pharyngitis|sore throat]], [[rhinitis|runny nose]], [[nasal congestion]], [[sneeze|sneezing]] and [[cough]]; sometimes accompanied by [[myalgia|muscle aches]], [[fatigue (medical)|fatigue]], [[malaise]], [[headache]], [[muscle weakness]], or [[Anorexia (symptom)|loss of appetite]]. [[Fever]] and extreme [[fatigue (medical)|exhaustion]] are less common in rhinovirus infection compared to [[influenza]], but rhinovirus can cause lower respiratory tract infection<ref>{{cite journal |last1=Papadopoulos |first1=Nikolaos G |title=Do rhinoviruses cause pneumonia in children? |journal=Paediatric Respiratory Reviews |date=2004 |volume=5 Suppl A |pages=S191–S195 |doi=10.1016/s1526-0542(04)90036-x |pmid=14980269}}</ref><ref>{{cite journal |last1=Hayden |first1=Frederick G |title=Rhinoviruses and the Lower Respiratory Tract |journal=Reviews in Medical Virology |date=2004 |volume=14 |issue=1 |pages=17–31 |doi=10.1002/rmv.406 |pmid=14716689 |pmc=7169234 }}</ref> and the pneumonia can, in young children, be fatal.<ref>{{cite journal |last1=Auvray |first1=C |last2=Perez-Martin |first2=S |last3=Schuffenecker |first3=I |last4=Pitoiset |first4=C |last5=Tarris |first5=G |last6=Ambert-Balay |first6=K |last7=Martin |first7=L |last8=Dullier-Taillefumier |first8=N |last9=Bour |first9=JB |last10=Manoha |first10=C |title=Sudden Infant Death Associated with Rhinovirus Infection |journal=Viruses |date=2024 |volume=16 |issue=4 |pages=518–527 |doi=10.3390/v16040518 |doi-access=free |pmid=38675861 |pmc=11054477 }}</ref>

== Epidemiology ==
Rhinoviruses can be detected year-round; however, the incidence of rhinovirus is higher in the autumn and winter, with most infections occurring between September and April in the northern hemisphere.<ref name="Moriyama_2020">{{cite journal | vauthors = Moriyama M, Hugentobler WJ, Iwasaki A | title = Seasonality of Respiratory Viral Infections | journal = Annual Review of Virology | volume = 7 | issue = 1 | pages = 83–101 | date = September 2020 | pmid = 32196426 | doi = 10.1146/annurev-virology-012420-022445 | s2cid = 214601321 | url = https://www.zora.uzh.ch/id/eprint/187834/1/annurev-virology-012420-022445.pdf }}</ref> The seasonality may be due to the start of the school year and to people spending more time indoors thereby increasing the chance of transmission of the virus.<ref>{{cite journal | vauthors = Fisman D | title = Seasonality of viral infections: mechanisms and unknowns | journal = Clinical Microbiology and Infection | volume = 18 | issue = 10 | pages = 946–954 | date = October 2012 | pmid = 22817528 | doi = 10.1111/j.1469-0691.2012.03968.x | doi-access = free }}</ref> Lower ambient temperatures, especially outdoors, may also be a factor given that rhinoviruses preferentially replicate at 33&nbsp;°C (91.4&nbsp;°F) as opposed to 37&nbsp;°C (98.6&nbsp;°F).<ref name="Moriyama_2020" /><ref name="Royston_2016">{{cite journal | vauthors = Royston L, Tapparel C | title = Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC | journal = Viruses | volume = 8 | issue = 1 | pages = 16 | date = January 2016 | pmid = 26761027 | pmc = 4728576 | doi = 10.3390/v8010016 | doi-access = free }}</ref> Other climate factors such as humidity may influence rhinovirus seasonality.<ref name="Moriyama_2020" /> Young children (<5 years old) experience a high rate of infection which can be detected in community surveillance studies of children up to 34% of the year.<ref>{{cite journal | vauthors = Kieninger E, Fuchs O, Latzin P, Frey U, Regamey N | title = Rhinovirus infections in infancy and early childhood | journal = The European Respiratory Journal | volume = 41 | issue = 2 | pages = 443–452 | date = February 2013 | pmid = 22743674 | doi = 10.1183/09031936.00203511 }}</ref> Phylogenetic analysis of rhinovirus strains in Nepalese infants revealed diverse lineages and patterns of virus circulation in low-resource settings.<ref>{{Cite journal |last1=Kuypers |first1=Jane |last2=Perchetti |first2=Garrett A. |last3=Chu |first3=Helen Y. |last4=Newman |first4=Kira L. |last5=Katz |first5=Joanne |last6=Khatry |first6=Subarna K. |last7=LeClerq |first7=Steven C. |last8=Jerome |first8=Keith R. |last9=Tielsch |first9=James M. |last10=Englund |first10=Janet A. |date=December 2019 |title=Phylogenetic characterization of rhinoviruses from infants in Sarlahi, Nepal |journal=Journal of Medical Virology |language=en |volume=91 |issue=12 |pages=2108–2116 |doi=10.1002/jmv.25563 |issn=0146-6615 |pmc=6800797 |pmid=31389049}}</ref> Those most affected by rhinoviruses are infants, the elderly, and [[immunocompromised]] people.<ref name="Jacobs Lamson et al 2013" /> 

== Pathogenesis ==
The primary route of entry for human rhinoviruses is the upper [[respiratory tract]] ([[mouth]] and [[nose]]). Rhinovirus A and B use "major" [[ICAM-1]] (Inter-Cellular Adhesion Molecule 1), also known as [[CD54]] (Cluster of Differentiation 54), on respiratory epithelial cells, as [[receptor (biochemistry)|receptors]] to bind to. Some subgroups under A and B use the "minor" [[LDL receptor]] instead.<ref name="Palmenberg2009">{{cite journal | vauthors = Palmenberg AC, Spiro D, Kuzmickas R, Wang S, Djikeng A, Rathe JA, Fraser-Liggett CM, Liggett SB | title = Sequencing and analyses of all known human rhinovirus genomes reveal structure and evolution | journal = Science | volume = 324 | issue = 5923 | pages = 55–59 | date = April 2009 | pmid = 19213880 | pmc = 3923423 | doi = 10.1126/science.1165557 | bibcode = 2009Sci...324...55P }}</ref> Rhinovirus C uses [[Cadherin related family member 3|cadherin-related family member 3 (CDHR3)]] to mediate cellular entry.<ref>{{cite journal | vauthors = Bochkov YA, Watters K, Ashraf S, Griggs TF, Devries MK, Jackson DJ, Palmenberg AC, Gern JE | title = Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 17 | pages = 5485–5490 | date = April 2015 | pmid = 25848009 | pmc = 4418890 | doi = 10.1073/pnas.1421178112 | doi-access = free | bibcode = 2015PNAS..112.5485B }}</ref> As the virus replicates and spreads, infected cells release distress signals known as [[chemokine]]s and [[cytokine]]s (which in turn activate inflammatory mediators).

Infection occurs rapidly, with the virus adhering to surface receptors within 15 minutes of entering the respiratory tract. Just over 50% of individuals will experience symptoms within 2 days of infection. Only about 5% of cases will have an [[incubation period]] of less than 20 hours, and, at the other extreme, it is expected that 5% of cases would have an [[incubation period]] of greater than four and a half days.<ref name=Lessler_2009b>{{cite journal | vauthors = Lessler J, Reich NG, Brookmeyer R, Perl TM, Nelson KE, Cummings DA | title = Incubation periods of acute respiratory viral infections: a systematic review | journal = The Lancet. Infectious Diseases | volume = 9 | issue = 5 | pages = 291–300 | date = May 2009 | pmid = 19393959 | pmc = 4327893 | doi = 10.1016/S1473-3099(09)70069-6 }}</ref>

Human rhinoviruses preferentially grow at 33&nbsp;°C (91.4&nbsp;°F), notably colder than the average human body temperature of 37&nbsp;°C (98.6&nbsp;°F), hence the virus's tendency to infect the [[upper respiratory tract]], where respiratory airflow is in continual contact with the (colder) extrasomatic environment.<ref name="Moriyama_2020" /><ref name="Royston_2016" />

Rhinovirus A and C species viruses are more strongly associated with significant illness and [[wheezing]], while rhinovirus B species are more commonly mild or asymptomatic.<ref name="Jacobs Lamson et al 2013" /><ref>{{cite journal | vauthors = Jackson DJ, Gern JE | title = Rhinovirus Infections and Their Roles in Asthma: Etiology and Exacerbations | journal = The Journal of Allergy and Clinical Immunology. In Practice | volume = 10 | issue = 3 | pages = 673–681 | date = March 2022 | pmid = 35074599 | pmc = 10314805 | doi = 10.1016/j.jaip.2022.01.006 }}</ref>

== Taxonomy ==
[[File:Phylogenetic analyses of HRV and HEV.jpg|thumb|[[Maximum likelihood]] [[phylogenetic tree]]s of enterovirus species A, B, C, D and rhinovirus A, B, C isolates from Latin America.  The [[5'UTR]] region is much more affected by recombination events than the VP4/VP2 [[coding sequence]].  The paraphyletic nature of "rhinovirus" is visible.<ref>{{cite journal | vauthors = Garcia J, Espejo V, Nelson M, Sovero M, Villaran MV, Gomez J, Barrantes M, Sanchez F, Comach G, Arango AE, Aguayo N, de Rivera IL, Chicaiza W, Jimenez M, Aleman W, Rodriguez F, Gonzales MS, Kochel TJ, Halsey ES | title = Human rhinoviruses and enteroviruses in influenza-like illness in Latin America | journal = Virology Journal | volume = 10 | pages = 305 | date = October 2013 | pmid = 24119298 | pmc = 3854537 | doi = 10.1186/1743-422x-10-305 | doi-access = free }}</ref>]]
The [[International Committee on Taxonomy of Viruses]] (ICTV) defines rhinoviruses as three species within the genus ''Enterovirus:''<ref>{{Cite journal |last1=Simmonds |first1=Peter |last2=Adriaenssens |first2=Evelien M. |last3=Lefkowitz |first3=Elliot J. |last4=Oksanen |first4=Hanna M. |last5=Siddell |first5=Stuart G. |last6=Zerbini |first6=Francisco Murilo |last7=Alfenas-Zerbini |first7=Poliane |last8=Aylward |first8=Frank O. |last9=Dempsey |first9=Donald M. |last10=Dutilh |first10=Bas E. |last11=Freitas-Astúa |first11=Juliana |last12=García |first12=María Laura |last13=Hendrickson |first13=R. Curtis |last14=Hughes |first14=Holly R. |last15=Junglen |first15=Sandra |date=2024-11-03 |title=Changes to virus taxonomy and the ICTV Statutes ratified by the International Committee on Taxonomy of Viruses (2024) |journal=Archives of Virology |language=en |volume=169 |issue=11 |pages=236 |doi=10.1007/s00705-024-06143-y |issn=1432-8798 |pmc=11532311 |pmid=39488803}}</ref>

* ''Enterovirus alpharhino'' (''Rhinovirus A'')

* ''Enterovirus betarhino'' (''Rhinovirus B'')
* ''Enterovirus cerhino'' (''Rhinovirus C'')

===Types===
Prior to 2020, enteroviruses (including all rhinoviruses) were categorized according to their [[serotype]]. In 2020 the ICTV ratified a proposal<ref name="pmid31980941">{{cite journal | vauthors = Simmonds P, Gorbalenya AE, Harvala H, Hovi T, Knowles NJ, Lindberg AM, Oberste MS, Palmenberg AC, Reuter G, Skern T, Tapparel C, Wolthers KC, Woo PC, Zell R | title = Recommendations for the nomenclature of enteroviruses and rhinoviruses | journal = Archives of Virology | volume = 165 | issue = 3 | pages = 793–797 | date = March 2020 | pmid = 31980941 | pmc = 7024059 | doi = 10.1007/s00705-019-04520-6 }}</ref> to classify all new types based on the genetic diversity of their VP1 gene.
Human rhinovirus type names are of the form '''RV-''Xn''''' where ''X'' is the rhinovirus species (A, B, or C) and ''n'' is an index number. Species A and B have used the same index up to number 100, while species C has always used a separate index. Valid index numbers are as follows:<ref name="ictv.global" />
* Rhinovirus A: 1, 1B, 2, 7–13, 15, 16, 18–25, 28–34, 36, 38–41, 43–47, 49–51, 53–68, 71, 73–78, 80–82, 85, 88–90, 94–96, 100–108
* Rhinovirus B: 3–6, 14, 17, 26, 27, 35, 37, 42, 48, 52, 69, 70, 72, 79, 83, 84, 86, 91–93, 97, 99, 100-104
* Rhinovirus C: 1–57

== Structure ==
[[File:Fmicb-08-02412-g001.jpg|thumb|Human rhinovirus genome, virion structure, and species]]
Rhinoviruses have single-stranded [[Positive-strand RNA virus|positive sense]] [[RNA]] genomes of between 7200 and 8500 [[nucleotide]]s in length. At the 5' end of the [[genome]] is a virus-encoded protein and, as in mammalian mRNA, there is a 3' [[poly-A tail]]. Structural proteins are encoded in the 5' region of the genome and non structural at the 3' end. This is the same for all [[picornavirus]]es. The viral particles themselves are not [[Viral envelope|enveloped]] and are [[dodecahedral]] in structure.

The viral proteins are translated as a single long [[polypeptide]], which is cleaved into the structural and nonstructural viral proteins.<ref>{{cite book |doi=10.1002/9780470015902.a0000431.pub3 |chapter=Rhinoviruses |title=eLS |year=2011 | vauthors = Arden KE, MacKay IM |isbn=978-0-470-01617-6 }}</ref>

The structure of the virus was determined in 1985 using [[x-ray crystallography]] by researchers at [[Purdue University]] and the [[University of Wisconsin]] led by [[Michael Rossmann]]. The virus was crystallized forming cubic crystals with four virus particles in each [[unit cell]] ([[space group]] ''P''2{{sub|1}}3, no. 198), similar to a [[cubic close-packed]] arrangement.<ref name=Rossmann_1985/>

Human rhinoviruses are composed of a [[capsid]] that contains four viral [[proteins]], VP1, VP2, VP3 and VP4.<ref name=Rossmann_1985>{{cite journal | vauthors = Rossmann MG, Arnold E, Erickson JW, Frankenberger EA, Griffith JP, Hecht HJ, Johnson JE, Kamer G, Luo M, Mosser AG | title = Structure of a human common cold virus and functional relationship to other picornaviruses | journal = Nature | volume = 317 | issue = 6033 | pages = 145–153 | year = 1985 | pmid = 2993920 | doi = 10.1038/317145a0 | s2cid = 4288590 | bibcode = 1985Natur.317..145R }}</ref><ref name=Smith_1986>{{cite journal | vauthors = Smith TJ, Kremer MJ, Luo M, Vriend G, Arnold E, Kamer G, Rossmann MG, McKinlay MA, Diana GD, Otto MJ | title = The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating | journal = Science | volume = 233 | issue = 4770 | pages = 1286–1293 | date = September 1986 | pmid = 3018924 | doi = 10.1126/science.3018924 | bibcode = 1986Sci...233.1286S }}</ref> VP1, VP2, and VP3 form the major part of the protein capsid. The much smaller VP4 protein has a more extended structure, and lies at the interface between the capsid and the RNA genome. There are 60 copies of each of these proteins assembled as an [[icosahedron]]. Antibodies are a major defense against infection with the [[epitopes]] lying on the exterior regions of VP1-VP3.

== Novel antiviral drugs ==
There are currently no FDA-approved [[antiviral drugs]] to treat rhinovirus infections.<ref name="www.cdc.gov_2023" /> Several novel antiviral compounds have been tested in clinical trials without sufficient efficacy to progress to FDA approval. Compounds specifically targeted for rhinoviruses, or more broadly, picornaviruses, include the following:

* [[Rupintrivir]] is a [[peptidomimetic]] drug developed for treatment of rhinovirus infections.<ref>{{cite journal | vauthors = Patick AK, Binford SL, Brothers MA, Jackson RL, Ford CE, Diem MD, Maldonado F, Dragovich PS, Zhou R, Prins TJ, Fuhrman SA, Meador JW, Zalman LS, Matthews DA, Worland ST | title = In vitro antiviral activity of AG7088, a potent inhibitor of human rhinovirus 3C protease | journal = Antimicrobial Agents and Chemotherapy | volume = 43 | issue = 10 | pages = 2444–2450 | date = October 1999 | pmid = 10508022 | pmc = 89498 | doi = 10.1128/AAC.43.10.2444 }}</ref> Rupintrivir inhibits human rhinovirus [[Picornain 3C|3Cprotease]] and prevents cleavage of the rhinovirus [[Proteolysis|polyprotein]] following translation, therefore preventing viral assembly and replication. A phase II clinical trial of rupintrivir using [[Human challenge study|experimentally induced rhinovirus infection]] in healthy volunteers demonstrated efficacy in reducing viral load and symptom severity. However, further trials testing rupintrivir in treating natural infections showed minimal benefit, and further clinical development was halted.<ref name="Coultas_2021">{{cite journal | vauthors = Coultas JA, Cafferkey J, Mallia P, Johnston SL | title = Experimental Antiviral Therapeutic Studies for Human Rhinovirus Infections | journal = Journal of Experimental Pharmacology | volume = 13 | pages = 645–659 | date = July 2021 | pmid = 34276229 | pmc = 8277446 | doi = 10.2147/JEP.S255211 | doi-access = free }}</ref>
* [[Pleconaril]] is an orally [[bioavailable]] antiviral drug developed for the treatment of infections caused by [[picornaviruses]].<ref name="Pevear_1999">{{cite journal | vauthors = Pevear DC, Tull TM, Seipel ME, Groarke JM | title = Activity of pleconaril against enteroviruses | journal = Antimicrobial Agents and Chemotherapy | volume = 43 | issue = 9 | pages = 2109–2115 | date = September 1999 | pmid = 10471549 | pmc = 89431 | doi = 10.1128/AAC.43.9.2109 }}</ref> This drug acts by binding to a hydrophobic pocket in VP1, and stabilizes the protein capsid to such an extent that the virus cannot release its RNA genome into the target cell. Phase III clinical trials showed a slight reduction in symptom duration if taken within 24 hours of symptom onset.<ref>{{cite journal | vauthors = Pevear DC, Hayden FG, Demenczuk TM, Barone LR, McKinlay MA, Collett MS | title = Relationship of pleconaril susceptibility and clinical outcomes in treatment of common colds caused by rhinoviruses | journal = Antimicrobial Agents and Chemotherapy | volume = 49 | issue = 11 | pages = 4492–4499 | date = November 2005 | pmid = 16251287 | pmc = 1280128 | doi = 10.1128/AAC.49.11.4492-4499.2005 }}</ref><ref name="Fleisher_2003">{{cite journal | vauthors = Fleischer R, Laessig K | title = Safety and efficacy evaluation of pleconaril for treatment of the common cold | journal = Clinical Infectious Diseases | volume = 37 | issue = 12 | pages = 1722 | date = December 2003 | pmid = 14689362 | doi = 10.1086/379830 | doi-access = free }}</ref> However, the FDA denied approval of pleconaril due to concerns about side effects, limited efficacy in non-white participants, and difficulty in treating most patients within a 24 hour window.<ref>{{cite journal | vauthors = Senior K | title = FDA panel rejects common cold treatment | journal = The Lancet. Infectious Diseases | volume = 2 | issue = 5 | pages = 264 | date = May 2002 | pmid = 12062983 | doi = 10.1016/s1473-3099(02)00277-3 }}</ref><ref>{{cite journal | vauthors = Moynihan R, Bero L, Ross-Degnan D, Henry D, Lee K, Watkins J, Mah C, Soumerai SB | title = Coverage by the news media of the benefits and risks of medications | journal = The New England Journal of Medicine | volume = 342 | issue = 22 | pages = 1645–1650 | date = June 2000 | pmc = 1126289 | doi = 10.1136/bmj.326.7403.1403 | pmid = 10833211 }}</ref>

Other treatments aiming to reduce rhinovirus infection symptoms include immunomodulatory agents. These may promote beneficial antiviral responses or reduce inflammatory responses associated with symptoms. [[Interferon type I|Interferon-alpha]] used intranasally was shown to be effective against human rhinovirus infections. However, volunteers treated with this drug experienced some side effects, such as nasal bleeding and began developing [[Drug tolerance|tolerance]] to the drug. Subsequently, research into the treatment was abandoned.<ref name="Farr">{{cite journal | vauthors = Farr BM, Gwaltney JM, Adams KF, Hayden FG | title = Intranasal interferon-alpha 2 for prevention of natural rhinovirus colds | journal = Antimicrobial Agents and Chemotherapy | volume = 26 | issue = 1 | pages = 31–34 | date = July 1984 | pmid = 6089652 | pmc = 179911 | doi = 10.1128/aac.26.1.31 }}</ref> Inhaled [[budesonide]] has been shown to reduce viral load and pro-inflammatory [[Interleukin 1 beta|IL-1β]] in mice. [[Omalizumab]], which was developed for treatment of severe allergic asthma, has shown evidence in reducing symptom severity of asthma patients infected with rhinovirus.<ref name="Coultas_2021" />

== Vaccine development ==
There are no [[vaccine]]s against these viruses as there is little-to-no cross-protection between [[serotype]]s. At least 165 types of human rhinoviruses are known.<ref name="ictv.global" /> However, a study of the VP4 protein has shown it to be highly conserved among many serotypes of human rhinovirus, opening up the potential for a future pan-serotype human rhinovirus vaccine.<ref>{{cite journal | vauthors = Katpally U, Fu TM, Freed DC, Casimiro DR, Smith TJ | title = Antibodies to the buried N terminus of rhinovirus VP4 exhibit cross-serotypic neutralization | journal = Journal of Virology | volume = 83 | issue = 14 | pages = 7040–7048 | date = July 2009 | pmid = 19403680 | pmc = 2704786 | doi = 10.1128/JVI.00557-09 }}</ref> A similar result was obtained with the VP1 protein. Like VP4, VP1 also occasionally "pokes" out of the viral particle, making it available to neutralizing antibodies. Both peptides have been tested on rabbits, resulting in successful generation of cross-serotype antibodies.<ref name=pmc4291752>{{cite journal | vauthors = Katpally U, Fu TM, Freed DC, Casimiro DR, Smith TJ | title = Antibodies to the buried N terminus of rhinovirus VP4 exhibit cross-serotypic neutralization | journal = Journal of Virology | volume = 83 | issue = 14 | pages = 7040–7048 | date = July 2009 | pmid = 19403680 | pmc = 4291752 | doi = 10.1128/JVI.00557-09 }}</ref>

Rhinovirus genome has a high rate of variability in human circulation, even occurring with genomic sequences that differ up to 30%.<ref>{{cite journal | vauthors = Ortega H, Nickle D, Carter L | title = Rhinovirus and asthma: Challenges and opportunities | journal = Reviews in Medical Virology | volume = 31 | issue = 4 | pages = e2193 | date = July 2021 | pmid = 33217098 | pmc = 8365703 | doi = 10.1002/rmv.2193 }}</ref> Recent studies have identified conserved regions of the rhinovirus genome; this, along with an adjuvanted polyvalent rhinovirus vaccine, shows potential for future development in vaccine treatment.<ref>{{cite journal | vauthors = Makris S, Johnston S | title = Recent advances in understanding rhinovirus immunity | journal = F1000Research | volume = 7 | page = 1537 | date = 24 September 2018 | pmid = 30345002 | pmc = 6173106 | doi = 10.12688/f1000research.15337.1 | doi-access = free }}</ref>

== Prevention ==
{{Main|Common cold#Prevention}}
Human rhinovirus can remain infectious for up to three hours outside of a human host. Once the virus is contracted, a person is most contagious within the first three days. Preventative measures such as regular vigorous [[handwashing]] with soap and water may aid in avoiding infection. Avoiding touching the mouth, eyes, and nose (the most common entry points for rhinovirus) may also assist prevention. Droplet precautions, which take the form of a surgical mask and gloves, are the method used in major hospitals.<ref>{{cite journal | vauthors = Siegel JD, Rhinehart E, Jackson M, Chiarello L | title = 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings | journal = American Journal of Infection Control | volume = 35 | issue = 10 Suppl 2 | pages = S65-164 | date = December 2007 | pmid = 18068815 | pmc = 7119119 | doi = 10.1016/j.ajic.2007.10.007 }}</ref> As with all respiratory pathogens once presumed to transmit via respiratory droplets, it is highly likely to be carried by the aerosols generated during routine breathing, talking, and even singing. In order to prevent airborne transmission, droplet precautions are insufficient, and routine airborne precautions are necessary.<ref name="prather_jimenez_marr_1">{{cite journal | vauthors = Wang CC, Prather KA, Sznitman J, Jimenez JL, Lakdawala SS, Tufekci Z, Marr LC | title = Airborne transmission of respiratory viruses | journal = Science | volume = 373 | issue = 6558 | date = August 2021 | pmid = 34446582 | pmc = 8721651 | doi = 10.1126/science.abd9149 }}</ref>

== References ==
{{Reflist}}

== External links ==
* [https://videos.med.wisc.edu/videos/1691 VIDEO: Rhinoviruses, the Old, the New and the UW] James E. Gern, MD, speaks at the University of Wisconsin School of Medicine and Public Health, 2008.
* [http://www.cellsalive.com/howbig.htm How Big is a Human rhinovirus? (animation)]

{{Baltimore classification}}
{{Common cold}}

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{{Authority control}}

[[Category:Crystals in space group 198]]
[[Category:Viral respiratory tract infections]]
[[Category:Enteroviruses]]