Bacillus Calmette-Guérin–induced trained immunity protects against SARS-CoV-2 challenge in K18-hACE2 mice

Zhang, Baozhong; Shuai, Huiping; Gong, Hua‐Rui; Hu, Jing-Chu; Yan, Bingpeng; Yuen, Terrence Tsz‐Tai; Hu, Ye-Fan; Yoon, Chaemin; Wang, Xiaolei; Hou, Yuxin; Lin, Xuansheng; Huang, Xiner; Li, Renhao; Au-Yeung, Yee Man; Li, Wenjun; Hu, Bingjie; Chai, Yue; Ming, Yue; Cai, Jian‐Piao; Ling, Guang Sheng; Hung, Ivan; Yuen, Kwok‐Yung; Chan, Jasper Fuk‐Woo; Huang, Jian‐Dong; Chu, Hin

doi:10.1172/jci.insight.157393

Cited by 36 publications

(32 citation statements)

References 73 publications

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“…Immunofluorescence staining was performed as we previously described ( 55 , 56 ). Briefly, infected hamster lungs were fixed for 24 hours in 10% formalin.…”

Section: Methodsmentioning

confidence: 99%

Altered host protease determinants for SARS-CoV-2 Omicron

Chan

Huang

et al. 2023

Sci. Adv.

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Successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires proteolytic cleavage of the viral spike protein. While the role of the host transmembrane protease serine 2 in SARS-CoV-2 infection is widely recognized, the involvement of other proteases capable of facilitating SARS-CoV-2 entry remains incompletely explored. Here, we show that multiple members from the membrane-type matrix metalloproteinase (MT-MMP) and a disintegrin and metalloproteinase families can mediate SARS-CoV-2 entry. Inhibition of MT-MMPs significantly reduces SARS-CoV-2 replication in vitro and in vivo. Mechanistically, we show that MT-MMPs can cleave SARS-CoV-2 spike and angiotensin-converting enzyme 2 and facilitate spike-mediated fusion. We further demonstrate that Omicron BA.1 has an increased efficiency on MT-MMP usage, while an altered efficiency on transmembrane serine protease usage for virus entry compared with that of ancestral SARS-CoV-2. These results reveal additional protease determinants for SARS-CoV-2 infection and enhance our understanding on the biology of coronavirus entry.

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“…Immunofluorescence staining was performed as we previously described ( 55 , 56 ). Briefly, infected hamster lungs were fixed for 24 hours in 10% formalin.…”

Section: Methodsmentioning

confidence: 99%

Altered host protease determinants for SARS-CoV-2 Omicron

Chan

Huang

et al. 2023

Sci. Adv.

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“…After inoculation, cells were washed by PBS before overlaying with 1% low-melting agarose, and further incubated for 72 h. Cells were fixed with 4% (wt/vol) paraformaldehyde, and plaque formation was visualized with 0.5% crystal violet in 25% ethanol. [23] Immunofluorescence and H&E Staining: After fixing for 24 h in 10% neutral-buffered formalin, mouse tissues were processed, paraffinized, and sectioned to prepare 4 μm tissue sections on glass slides. After de-waxing, antigen retrieval was performed.…”

Section: Methodsmentioning

confidence: 99%

Engineered Intranasal Virus Trap Provides Effective Protection Against SARS‐CoV‐2 Infection in Hamsters

Au‐Yeung,

Zhang,

Chen

et al. 2023

Adv Funct Materials

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As face masks are no longer required in many public areas, SARS‐CoV‐2 continues to spread and pose health risks to vulnerable populations such as children, the elderly, and immunocompromised individuals. This study presents the development of an Fn‐LCB1‐based engineered intranasal virus trap (EIVT) designed to capture and neutralize multiple SARS‐CoV‐2 variants, limiting viral infection and transmission. Fn‐LCB1, a fusion protein consisting of an Fn domain that binds to fibronectin and an LCB1 domain with high affinity for the Spike protein receptor‐binding domain (RBD) of SARS‐CoV‐2 viruses, can be produced on a large scale and purified in soluble form with high thermal stability. In vitro experiments demonstrated the efficient neutralization of SARS‐CoV‐2 wildtype and several variants, including Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529) by Fn‐LCB1. Additionally, Fn‐LCB1 effectively protected against SARS‐CoV‐2 Delta infection in a noncontact viral transmission Syrian hamster model. This study establishes Fn‐LCB1 as a potent prophylactic agent against SARS‐CoV‐2 in vitro and in vivo, and serves as a proof‐of‐concept for the application of intranasal proteins to capture respiratory viruses and reduce live cell infections by competing with viral receptors.

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“…Plaque assay was performed as we described previously [40,41]. Briefly, hamster lung tissues were harvested and homogenized in DMEM using the Tissue Lyzer II (Qiagen, Germany).…”

Section: Infectious Viral Titer By Plaque Assaymentioning

confidence: 99%

Targeting ACLY efficiently inhibits SARS-CoV-2 replication

Yuen¹,

Chan²,

Yan³

et al. 2022

Int. J. Biol. Sci.

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The Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the biggest public health challenge the world has witnessed in the past decades. SARS-CoV-2 undergoes constant mutations and new variants of concerns (VOCs) with altered transmissibility, virulence, and/or susceptibility to vaccines and therapeutics continue to emerge. Detailed analysis of host factors involved in virus replication may help to identify novel treatment targets. In this study, we dissected the metabolome derived from COVID-19 patients to identify key host factors that are required for efficient SARS-CoV-2 replication. Through a series of metabolomic analyses, in vitro, and in vivo investigations, we identified ATP citrate lyase (ACLY) as a novel host factor required for efficient replication of SARS-CoV-2 wild-type and variants, including Omicron. ACLY should be further explored as a novel intervention target for COVID-19.

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Bacillus Calmette-Guérin–induced trained immunity protects against SARS-CoV-2 challenge in K18-hACE2 mice

Cited by 36 publications

References 73 publications

Altered host protease determinants for SARS-CoV-2 Omicron

Altered host protease determinants for SARS-CoV-2 Omicron

Engineered Intranasal Virus Trap Provides Effective Protection Against SARS‐CoV‐2 Infection in Hamsters

Targeting ACLY efficiently inhibits SARS-CoV-2 replication

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