Host and viral determinants for efficient SARS-CoV-2 infection of the human lung

Chu, Hin; Hu, Bingjie; Huang, Xiner; Chai, Yue; Wang, Yixin; Shuai, Huiping; Yang, Dong; Hou, Yuxin; Zhang, Xi; Yuen, Terrence Tsz‐Tai; Cai, Jian‐Piao; Zhang, Anna Jinxia; Zhou, Jie; Ong, Chon Phin; To, Kelvin Kai‐Wang; Chan, Iris Hiu-Shuen; Sit, Ko‐Yung; Foo, Chi Chung; Wong, Ian Yu‐Hong; Ng, Anthony Chin-Ki; Cheung, Tan To; Law, Simon; Au, Wing-Kuk; Kok, Kin‐Hang; Chan, Jasper Fuk‐Woo; Yuen, Kwok‐Yung

doi:10.21203/rs.3.rs-40123/v1

Cited by 34 publications

(52 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed that decrease in viral loads coincided with increase in IFN responses which is in agreement with observations made by other groups in ex vivo, cell culture and animal models where SARS-CoV-2 was shown to be a more potent inhibitor of IFN responses than SARS-CoV-1 (29,30). Although our study does not have relative comparison between samples from different severities, we observed a consistent decrease in type I and type II during the acute phase of infection.…”

Section: Zinc Supplementation Affects Sars-cov-2 Infection In Vitrosupporting

confidence: 92%

Kinetics of viral load, immunological mediators and characterization of a SARS-CoV-2 isolate in mild COVID-19 patients during acute phase of infection

Anantharaj

Gujjar

Kumar

et al. 2020

Preprint

View full text Add to dashboard Cite

Over 95% of the COVID-19 cases are mild-to-asymptomatic who contribute to disease transmission whereas most of the severe manifestations of the disease are observed in elderly and in patients with comorbidities and dysregulation of immune response has been implicated in severe clinical outcomes. However, it is unclear whether asymptomatic or mild infections are due to low viral load or lack of inflammation. We have measured the kinetics of SARS-CoV-2 viral load in the respiratory samples and serum markers of inflammation in hospitalized COVID-19 patients with mild symptoms. We observed a bi-phasic pattern of virus load which was eventually cleared in most patients at the time of discharge. Viral load in saliva samples from a subset of patients showed good correlation with nasopharyngeal samples. Serum interferon levels were downregulated during early stages of infection but peaked at later stages correlating with elevated levels of T-cell cytokines and other inflammatory mediators such as IL-6 and TNF-alpha which showed a bi-phasic pattern. The clinical recovery of patients correlated with decrease in viral load and increase in interferons and other cytokines which indicates an effective innate and adaptive immune function in mild infections. We further characterized one of the SARS-CoV-2 isolate by plaque purification and show that infection of lung epithelial cells (Calu-3) with this isolate led to cytopathic effect disrupting epithelial barrier function and tight junctions. Finally we showed that zinc was capable of inhibiting SARS-CoV-2 infection in this model suggesting a beneficial effect of zinc supplementation in COVID-19 infection.

show abstract

Section: Zinc Supplementation Affects Sars-cov-2 Infection In Vitrosupporting

confidence: 92%

Kinetics of viral load, immunological mediators and characterization of a SARS-CoV-2 isolate in mild COVID-19 patients during acute phase of infection

Anantharaj

Gujjar

Kumar

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The glycosylation processing state can influence immunogen trafficking in the lymphatic system 10 , influence the presentation of both native and unwanted cryptic epitopes 11 , and reveal to what extent immunogens recapitulate native viral architecture. Evidence is also emerging that glycosylation can somewhat influence the interaction between SARS-CoV-2 and its target receptor, angiotensin converting enzyme 2 (ACE2) [12][13][14][15] . The SARS-CoV-2 S protein contains at least sixty-six N-linked glycosylation sequons that direct the attachment of host glycans to specific Asn residues.…”

Section: Introductionmentioning

confidence: 99%

Site-specific steric control of SARS-CoV-2 spike glycosylation

Allen

Chawla

Samsudin

et al. 2021

Preprint

View full text Add to dashboard Cite

A central tenet in the design of recombinant vaccines is the display of native-like antigens in the elicitation of protective immunity. However, the diversity of global vaccine strategies against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses challenges to benchmark antigens across global vaccine programs. Here, we investigate the glycosylation of a variety of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against the glycan shield of an infectious virus. The site-specific stalling of glycan maturation is a highly sensitive reporter of local protein structure and we find there is remarkable conservation of this feature across all samples. Analysis of molecular dynamics simulations of a fully glycosylated spike supports a model of steric restrictions that shape enzymatic processing of the glycans. Furthermore, we show that there is a conserved glycosylation pattern across the monomeric receptor binding domain (RBD) protein and the complete trimeric spike (S) protein. This is in contrast to RBD glycosylation in Middle East respiratory syndrome coronavirus (MERS-CoV) where quaternary architecture limits glycan processing when in the context of full-length MERS-CoV S protein. These results suggest that spike-based immunogen glycosylation reproducibly recapitulates viral glycosylation.

show abstract

“…Stages of the replication cycle of SARS-CoV-2 have been rapidly inferred from empirical data and extant knowledge of other betacoronaviruses. The first step in cellular infection by SARS-CoV-2 is the binding of S protein to the host cell surface entry factors such as the membrane associated and soluble ACE2 receptor [ 38 ] which may be preceded by weaker binding of the S protein to attachment factors such as heparan sulphate [ 39 ]. Other entry factors that facilitate attachment or entry include neuropilin-1 [ 40 , 41 ], the tyrosine-protein kinase receptor UFO (AXL) [ 42 ], CD147 [ 43 ], high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) [ 44 ], integrins [ 45 , 46 ], angiotension II receptor 1 (AT1) and vasopressin receptor 2, but their role in natural infection is currently unclear.…”

Section: Taxonomy Genomic Organization and Replication Cycle Of Sarmentioning

confidence: 99%

Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic

Sridhar

Chiu

et al. 2021

Emerging Microbes & Infections

Self Cite

227

145

View full text Add to dashboard Cite

Without modern medical management and vaccines, the severity of the Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome(SARS) coronavirus 2 (SARS-CoV-2) might approach the magnitude of 1894-plague (12 million deaths) and 1918-A(H1N1) influenza (50 million deaths) pandemics. The COVID-19 pandemic was heralded by the 2003 SARS epidemic which led to the discovery of human and civet SARS-CoV-1, bat SARS-related-CoVs, Middle East respiratory syndrome(MERS)-related bat CoV HKU4 and HKU5, and other novel animal coronaviruses. The suspected animal-to-human jumping of 4 betacoronaviruses including the human coronaviruses OC43(1890), SARS-CoV-1(2003), MERS-CoV(2012), and SARS-CoV-2(2019) indicates their significant pandemic potential. The presence of a large reservoir of coronaviruses in bats and other wild mammals, culture of mixing and selling them in urban markets with suboptimal hygiene, habit of eating exotic mammals in highly populated areas, and the rapid and frequent air traffic from these areas are perfect ingredients for brewing rapidly exploding epidemics. The possibility of emergence of a hypothetical SARS-CoV-3 or other novel viruses from animals or laboratories, and therefore needs for global preparedness should not be ignored. We reviewed representative publications on the epidemiology, virology, clinical manifestations, pathology, laboratory diagnostics, treatment, vaccination and infection control of COVID-19 as of 20 January 2021, which is one year after person-to-person transmission of SARS-CoV-2 was announced. The difficulties of mass testing, labour-intensive contact tracing, importance of compliance to universal masking, low efficacy of antiviral treatment for severe disease, possibilities of vaccine or antiviral-resistant virus variants and SARS-CoV-2 becoming another common cold coronavirus are discussed. The chronology of the pandemic An outbreak of acute community-acquired atypical pneumonia of unknown aetiology was reported in Wuhan, the capital of Hubei province in central China, in December 2019. The initial cluster of cases was related to the Huanan seafood wholesale market where wild game animals were also sold (1). During subsequent investigation, severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) was detected in 33 out of 585 environmental samples taken from the market (2). However, 45% of the cases with onset before 1 January 2020 had no apparent link to this market (3). Retrospective molecular clock inference studies using phylogenetic analysis suggested that the earliest cases likely emerged between October and November 2019 (4, 5). The culprit virus was identified using next-generation sequencing on bronchoalveolar lavage fluids of three Wuhan patients (6). The complete genome sequences of SARS-CoV-2 clustered in a distinct clade from SARS-CoV within the genus Sarbecovirus. The draft genome sequence was released on 10 Jan 2020, 10 days after the outbreak was announced. As an escalating number of local cases was reported in Wuhan, a f...

show abstract

Host and viral determinants for efficient SARS-CoV-2 infection of the human lung

Cited by 34 publications

References 49 publications

Kinetics of viral load, immunological mediators and characterization of a SARS-CoV-2 isolate in mild COVID-19 patients during acute phase of infection

Kinetics of viral load, immunological mediators and characterization of a SARS-CoV-2 isolate in mild COVID-19 patients during acute phase of infection

Site-specific steric control of SARS-CoV-2 spike glycosylation

Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic

Contact Info

Product

Resources

About