Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic

Boni, Maciej F.; Lemey, Philippe; Jiang, Xiaowei; Lam, Tommy Tsan Yuk; Perry, Blair W.; Castoe, Todd A.; Rambaut, Andrew; Robertson, David L.

doi:10.1038/s41564-020-0771-4

Cited by 852 publications

(707 citation statements)

References 63 publications

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“…The current outbreak of SARS-CoV-2, a novel coronavirus with a yet undetermined origin, causes an unprecedented threat to modern societies 5,79,80 . Due to the WHO declared SARS-CoV-2 pandemic, intense research is being manifested to deliver speci c medicines halting virus spread and infection 12 .…”

Section: Discussionmentioning

confidence: 99%

“…The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is beta-coronavirus initially emerging in China and then rapidly spreading throughout the world, becoming a signi cant threat to human health [1][2][3][4][5][6][7][8] . On 13 March, the WHO declared Europe the epicenter of the SARS-CoV-2 pandemic 9 .…”

Section: Introductionmentioning

confidence: 99%

“…Coronaviruses are endowed with a high tendency to spread from animals to humans, hence enabling cross-species transmission and facilitating severe outbreaks 5,[16][17][18][19] . The capacity of coronaviruses for cross-species transmission also supports the need to develop highly e cient, yet safe therapeutics and prophylactics to tackle current and future pandemics 6,[20][21][22] .…”

Section: Introductionmentioning

confidence: 99%

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Contribution of syndecans to the cellular entry of SARS-CoV-2

Hudák

Szilák

Letoha

2020

Preprint

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel emerging pathogen causing an unprecedented pandemic in 21st century medicine. Due to the significant health and economic burden of the current SARS-CoV-2 outbreak, there is a huge unmet medical need for novel interventions effectively blocking SARS-CoV-2 infection. Unknown details of SARS-CoV-2 cellular biology significantly hamper the development of potent and highly specific SARS-CoV-2 therapeutics. Angiotensin-converting enzyme-2 (ACE2) has been reported to be the primary receptor for SARS-CoV-2 cellular entry. However, emerging scientific evidence suggests the involvement of additional membrane proteins, such as heparan sulfate proteoglycans, in SARS-CoV-2 internalization. Here we report that syndecans, the evolutionarily conserved family of transmembrane proteoglycans facilitate the cellular entry of SARS-CoV-2. Among syndecans, syndecan-4 was the most efficient in mediating SARS-CoV-2 uptake, yet overexpression of other isoforms, including the neuronal syndecan-3, also increased SARS-CoV-2 internalization. The S1 subunit of the SARS-CoV-2 spike protein plays a dominant role in the virus’s interactions with syndecans. Besides the polyanionic heparan sulfate chains - the established binding sites for several viruses - other parts of the syndecan ectodomain, such as the cell-binding domain, also contribute to the interaction with SARS-CoV-2. During virus internalization, syndecans colocalize with ACE2, suggesting a jointly shared internalization pathway. Both ACE2 and syndecan inhibitors exhibited significant efficacy in reducing cellular entry of SARS-CoV-2, thus supporting the complex nature of internalization. Among these inhibitors, a peptide compromising the spike protein’s heparin-binding PRRAR motif significantly reduced SARS-CoV-2 cellular uptake, highlighting the need to go beyond the ACE2 paradigm for developing efficient therapeutics against SARS-CoV-2. Data obtained on syndecan specific in vitro assays present syndecans as novel cellular targets of SARS-CoV-2 and offers molecularly precise, yet simple strategies in overcoming the complex nature of SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Contribution of syndecans to the cellular entry of SARS-CoV-2

Hudák

Szilák

Letoha

2020

Preprint

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“…They also include a substantial diversity of SARS-related coronaviruses that include the progenitor lineages of SARS-CoV and SARS-CoV-2, primarily carried by horseshoe bats (Rhinolophus spp.) [68][69][70][71][72][73] . SARS-CoV emerged in 2002 within urban live animal markets in Guangdong, where a range of animal species being held there, as well as animal vendors themselves, were infected 74 .…”

Section: Discussionmentioning

confidence: 99%

“…SARS-CoV emerged in 2002 within urban live animal markets in Guangdong, where a range of animal species being held there, as well as animal vendors themselves, were infected 74 . While the exact route of SARS-CoV-2 spillover from bats to humans is uncertain, evidence strongly implicates a similar live animal market as a site where infections were ampli ed, and where SARS-CoV-2 was identi ed on contaminated surfaces 68,75 . Subsequent clusters of COVID-19 have been reported in a large seafood market in Beijing, perhaps as a direct result of contamination of cold surfaces used to prepare food 76 .…”

Section: Discussionmentioning

confidence: 99%

Microbicidal actives with virucidal efficacy against SARS-CoV-2 and other beta- and alpha-coronaviruses: implications for future emerging coronaviruses and other enveloped viruses

Ijaz

Nims²,

Zhou³

et al. 2020

Preprint

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Mitigating the risk of acquiring SARS-CoV-2 or other coronaviruses requires awareness of the survival of virus on high-touch environmental surfaces (HITES) and skin, and frequent use of targeted microbicides with virucidal efficacy. We evaluated the efficacies of formulated microbicidal actives against alpha- and beta-coronaviruses, including SARS-CoV-2.Infectious coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, human coronavirus 229E, bovine coronavirus, murine hepatitis virus-1, and Middle East respiratory syndrome coronavirus, were deposited on prototypic HITES or spiked into liquid matrices along with organic soil loads. Alcohol-, quaternary ammonium compound-, hydrochloric acid-, organic acid-, p-chloro-m-xylenol-, and sodium hypochlorite-based microbicidal formulations were evaluated per global standardized ASTM International and EN methodologies. All evaluated formulated microbicides inactivated SARS-CoV-2 and other coronaviruses in suspension or on prototypic HITES. Virucidal efficacies ( ≥3 to ≥6 log10 reduction) were displayed within 30 s to 5 min. Coronaviruses, like other lipid-enveloped viruses, are susceptible to commonly used microbicides. We confirmed the virucidal efficacy of a variety of commercially available formulated microbicides against SARS-CoV-2 and other coronaviruses. These formulated microbicidal actives should be useful for targeted surface and hand hygiene and disinfection of liquids, as part of infection prevention and control for SARS-CoV-2 and other emerging enveloped viruses.

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