Metabolites with SARS-CoV-2 Inhibitory Activity Identified from Human Microbiome Commensals

Piscotta, Frank J.; Hoffmann, Hans-Heinrich; Choi, Young Joo; Small, Gabriel I.; Koirala, Bimal; Campbell, Elizabeth A.; Darst, Seth A.; Rice, Charles M.

doi:10.1128/msphere.00711-21

Cited by 23 publications

(12 citation statements)

References 57 publications

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“…Interestingly, a recent systematic literature review concluded that butyrate inhibits SARS-CoV-2 infectivity by reducing the expression the of ACE2 and TMPRSS2 genes, upregulating the level of ADAM17, a metallopeptidase involved in ACE2 shedding, and upregulating multiple critical antiviral pathways such as TLR (Li J. et al, 2021). Three bacterial metabolites 5-hydroxytryptamine receptor agonist tryptamine, pyrazine 2,5-bis (3-indolylmethyl) pyrazine and N6-(D2isopentenyl) adenosine, exert anti-SARS-CoV-2 activity and share the similar structures and functions to clinical antiviral drugs (Piscotta et al, 2021). High doses of 25-hydroxyvitamin D notably reduced ICU admission for hospitalized patients with COVID-19 (Entrenas Castillo et al, 2020).…”

Section: Relationship Between Microbial Metabolites and Covid-19mentioning

confidence: 99%

Microbiota and COVID-19: Long-term and complex influencing factors

Gang

Xue

et al. 2022

Front. Microbiol.

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The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the World Health Organization statistics, more than 500 million individuals have been infected and more than 6 million deaths have resulted worldwide. Although COVID-19 mainly affects the respiratory system, considerable evidence shows that the digestive, cardiovascular, nervous, and reproductive systems can all be involved. Angiotensin-converting enzyme 2 (AEC2), the target of SARS-CoV-2 invasion of the host is mainly distributed in the respiratory and gastrointestinal tract. Studies found that microbiota contributes to the onset and progression of many diseases, including COVID-19. Here, we firstly conclude the characterization of respiratory, gut, and oral microbial dysbiosis, including bacteria, fungi, and viruses. Then we explore the potential mechanisms of microbial involvement in COVID-19. Microbial dysbiosis could influence COVID-19 by complex interactions with SARS-CoV-2 and host immunity. Moreover, microbiota may have an impact on COVID-19 through their metabolites or modulation of ACE2 expression. Subsequently, we generalize the potential of microbiota as diagnostic markers for COVID-19 patients and its possible association with post-acute COVID-19 syndrome (PACS) and relapse after recovery. Finally, we proposed directed microbiota-targeted treatments from the perspective of gut microecology such as probiotics and prebiotics, fecal transplantation and antibiotics, and other interventions such as traditional Chinese medicine, COVID-19 vaccines, and ACE2-based treatments.

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Section: Relationship Between Microbial Metabolites and Covid-19mentioning

confidence: 99%

Microbiota and COVID-19: Long-term and complex influencing factors

Gang

Xue

et al. 2022

Front. Microbiol.

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“…Several antiviral agents against SARS-CoV-2 have been developed, however, their efficacy is variable and often dependent upon intervening before the need for intervention is clear. A series of different biomolecules have been proposed as treatments and recently, 3 metabolites produced by components of the human microbiome were shown to be active against SARS-CoV-2 in vitro [22,23].…”

Section: Plos Onementioning

confidence: 99%

Few SARS-CoV-2 infections detected in Newfoundland and Labrador in the absence of Public Health Laboratory-based confirmation

et al. 2022

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Objective To assess the incidence of COVID-19 infection in the absence of a confirmatory test in persons suspecting they contracted COVID-19 and elucidate reasons for their belief. Methods We recruited persons with a confirmed COVID-19 diagnosis and persons who believed they may have contracted COVID-19 between December, 2019 and April, 2021 into a study of immunity against SARS-CoV-2. An intake questionnaire captured their perceived risk factors for exposure and symptoms experienced, including symptom duration and severity. ELISA testing against multiple SARS-CoV-2 antigens was done to detect antibodies against SARS-CoV-2. No participant had received COVID-19 vaccination prior to the time of testing. Results The vast majority of study subjects without Public Health confirmation of infection had no detectable antibodies against SARS-CoV-2. Suspected infection with SARS-CoV-2 generally involved experiencing symptoms common to many other respiratory infections. Unusually severe or persistent symptoms often supported suspicion of infection with SARS-CoV-2 as did travel or contact with travelers from outside Newfoundland and Labrador. Rare cases in which antibodies against SARS-CoV-2 were detected despite negative results of Public Health testing for SARS-CoV-2 RNA involved persons in close contact with confirmed cases. Conclusions Broad public awareness and declaration of pandemic status in March, 2020 contributed to the perceived risk of contracting COVID-19 in Newfoundland and Labrador from late 2019 to April 2021 and raised expectation of its severity. Serological testing is useful to diagnose past infection with SARS-CoV-2 to accurately estimate population exposure rates.

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“…Given the associations between gut microbiota and cardiometabolic outcomes, developing new therapeutic strategies targeting the gut microbial communities is a promising approach to prevent or treat these diseases. Considerable effort into developing strategies has been used to achieve this goal [ 179 ], including prebiotics [ 180 , 181 ], probiotics [ [182] , [183] , [184] ], fecal microbiota transplantation [ 185 , 186 ], metabolites [ [187] , [188] , [189] , [190] , [191] ], phages [ 192 , 193 ], miRNAs [ 194 ], and hyaluronan [ 195 , 196 ]. In particular, studies in mice have demonstrated that transplantation of cecal microbes from an atherosclerosis-prone strain with high TMA/TMAO levels to a low TMAO-producing and atherosclerosis-resistant strain can enhance production of these pro-atherogenic metabolites with a corresponding increase in aortic lesion formation [ 197 ].…”

Section: Summary and Future Prospectsmentioning

confidence: 99%