Neuropilin-1 is a host factor for SARS-CoV-2 infection

Daly, James L.; Simonetti, Boris; Klein, Katja; Chen, Kai‐En; Williamson, Maia Kavanagh; Antón-Plágaro, Carlos; Shoemark, Deborah K.; Simón‐Gracia, Lorena; Bauer, Michael; Hollandi, Réka; Greber, Urs F.; Horváth, Péter; Sessions, Richard B.; Helenius, Ari; Hiscox, Julian A.; Teesalu, Tambet; Matthews, David A.; Davidson, Andrew D.; Collins, Brett M.; Cullen, Peter J.; Yamauchi, Yohei

doi:10.1126/science.abd3072

Cited by 1,060 publications

(950 citation statements)

References 33 publications

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“…The C-terminal sequence may allow the protein to associate with cell surface NRP1 and NRP2 receptors. A recent finding suggests that NRP1 may serve as a host factor for SARS-CoV-2 infection, which is very abundant in many human tissues including the respiratory tract, blood vessels, and neurons [57]. NRP1 significantly potentiates SARS-CoV-2 infectivity.…”

Section: New Mediator Associated With Sars-cov-2 Viral Entry: Neuropimentioning

confidence: 99%

“…NRP1 significantly potentiates SARS-CoV-2 infectivity. Daly et al [57] showed that blocking the binding between NRP1 and C-end rule (CendR) motif in S1 (with RNAi or selective inhibitors), play a role in the increased infectivity of SARS-CoV-2 compared with SARS-CoV. They observed in cells with both the ACE2 and neuropilin-1 proteins, SARS-CoV-2 infection was greater compared to cells with either "doorway" alone.…”

Section: New Mediator Associated With Sars-cov-2 Viral Entry: Neuropimentioning

confidence: 99%

See 1 more Smart Citation

ACE2: the molecular doorway to SARS-CoV-2

Medina-Enríquez

López-Léon²,

Carlos-Escalante

et al. 2020

Cell Biosci

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The angiotensin-converting enzyme 2 (ACE2) is the host functional receptor for the new virus SARS-CoV-2 causing Coronavirus Disease 2019. ACE2 is expressed in 72 different cell types. Some factors that can affect the expression of the ACE2 are: sex, environment, comorbidities, medications (e.g. anti-hypertensives) and its interaction with other genes of the renin-angiotensin system and other pathways. Different factors can affect the risk of infection of SARS-CoV-2 and determine the severity of the symptoms. The ACE2 enzyme is a negative regulator of RAS expressed in various organ systems. It is with immunity, inflammation, increased coagulopathy, and cardiovascular disease. In this review, we describe the genetic and molecular functions of the ACE2 receptor and its relation with the physiological and pathological conditions to better understand how this receptor is involved in the pathogenesis of COVID-19. In addition, it reviews the different comorbidities that interact with SARS-CoV-2 in which also ACE2 plays an important role. It also describes the different factors that interact with the virus that have an influence in the expression and functional activities of the receptor. The goal is to provide the reader with an understanding of the complexity and importance of this receptor.

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Section: New Mediator Associated With Sars-cov-2 Viral Entry: Neuropimentioning

confidence: 99%

Section: New Mediator Associated With Sars-cov-2 Viral Entry: Neuropimentioning

confidence: 99%

ACE2: the molecular doorway to SARS-CoV-2

Medina-Enríquez

López-Léon²,

Carlos-Escalante

et al. 2020

Cell Biosci

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“…Recent work showed that the NTD of SARS-CoV-2 may bind cellular receptors other than ACE2 and mediate the entry of the virus into cells that do not express ACE2 [35]. Furthermore, the cell-surface protein neuropilin-1 has been reported to facilitate SARS-CoV-2 cell entry, especially into brain cells [36][37][38], although the mechanism is not fully understood.…”

Section: The Spike Glycoproteinmentioning

confidence: 99%

Spike Glycoprotein-Mediated Entry of SARS Coronaviruses

Wang

Xiang

2020

Viruses

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Severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 are enveloped, positive-sense, single-stranded RNA viruses and causes of epidemic diseases that have resulted in public health emergencies worldwide. Angiotensin-converting enzyme 2 (ACE2) is the receptor that allows the entry of these two viruses into host cells, a key step in the life cycle of the pathogens. The characterization of the interactions of ACE2 with the viral spike glycoproteins and structural studies of the ACE2-binding-induced conformational changes in the viral spike glycoproteins have furthered our understanding of the entry processes of these two viruses, and these studies provide useful information that will facilitate the development of antiviral agents and vaccines to control the diseases.

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“…We urge readers to refer to original articles, reviews and professional guidelines and COVID-19 resources. (22,(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53) Conclusion SARS-CoV-2-2019-the most pathogenic killer virushas created an unprecedented, once in a century syndemic. Currently, global COVID-19 positive cases exceed 43,623,111 with 1,161,311 deaths.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Biochemistry, Transmission, Clinical Manifestations, and Prevention

Rao¹

2020

IJBM

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The first human case of COVID-19, caused by the novel coronavirus, was reported by health officials in the city of Wuhan, China, in December of 2019. The virus was identified as a novel coronavirus in early January 2020, and its genetic sequence was shared publicly on January 11, 2020. The novel virus, previously called 2019-novel coronavirus (2019-nCoV), is currently designated as the severe respiratory syndrome coronavirus-2 (SARS-CoV-2). On January 23, Wuhan was locked down, and the World Health Organization (WHO) declared a “public health emergency of international concern.” The viral genome of SARS-CoV-2 is around 29.8 kilobase, containing six major open reading frames. The most common clinical symptoms were fever, cough, fatigue, shortness of breath, dyspnea, muscle ache, headache, chest pain, vomiting, sore throat, and sputum production. The main mode of transmission is through respiratory particles. The incubation period is 3 to 7 days. Both asymptomatic and symptomatic patients seem to be infectious. Spike (S) proteins of SARS-CoV-2 seem to have a 10- to 20-fold higher affinity to the human angiotensin enzyme 2 (ACE2) receptor than that of SARS-CoV. The high affinity of S protein to theACE2 receptor, and the additional advantages offered by the transfection facilitators Furin and Neutropilin-1, likely, contributes to the rapid spreading of this novel virus. Since these receptors are highly expressed on a variety of cells, including vascular endothelial cells and adipose tissue, individuals with compromised function of these tissues drive greater infection and severity in patients with COVID-19. Global health experts estimate that one in five individuals worldwide could be at risk for severe COVID-19, due to underlying health conditions. There is a great need for a rapid, specific, cost-effective test for monitoring the infected individuals. Even though a 15- minute, antigen test was made available by Abbott recently, it seems that the schools, colleges, and business establishments lack the ability to use these tests effectively to keep their businesses open safely. Management of the infected individuals seems to be based on clinical symptoms that manifest as the disease progresses. The US Food & Drug Administration (FDA), has created a special emergency program for possible therapies, the Coronavirus Treatment Acceleration Program (CTAP). The program uses every available method to move new and emerging treatments as quickly as possible, keeping in mind the safety and efficacy of such therapies. According to the WHO report, there are currently more than 150 COVID-19 vaccine candidates under development. Several vaccines are in Phase 3 clinical trials. In an unprecedented effort, one of the experimental monoclonal antibody cocktails of Regeneron was used for therapeutic purposes when the US president was tested positive for COVID-19. There are no drugs or other therapeutics approved by the US FDA to prevent or treat COVID-19. The National Institutes of Health (NIH) have published interim guidelines for the medical management of COVID-19. In the absence of a cure, the only choice we all have is to follow the best practices recommended by the public health experts—use of face masks (coverings), frequent hand washing with soap, contact tracing of infected individuals, and quarantining COVID-19 positive individuals, till they are free of the highly infectious virus.

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Neuropilin-1 is a host factor for SARS-CoV-2 infection

Cited by 1,060 publications

References 33 publications

ACE2: the molecular doorway to SARS-CoV-2

ACE2: the molecular doorway to SARS-CoV-2

Spike Glycoprotein-Mediated Entry of SARS Coronaviruses

SARS-CoV-2 Biochemistry, Transmission, Clinical Manifestations, and Prevention

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