PMID- 35164139
OWN - NLM
STAT- MEDLINE
DCOM- 20220218
LR  - 20221207
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 27
IP  - 3
DP  - 2022 Jan 27
TI  - A New Butyrate Releaser Exerts a Protective Action against SARS-CoV-2 Infection 
      in Human Intestine.
LID - 10.3390/molecules27030862 [doi]
LID - 862
AB  - Butyrate is a major gut microbiome metabolite that regulates several defense 
      mechanisms against infectious diseases. Alterations in the gut microbiome, 
      leading to reduced butyrate production, have been reported in patients with 
      severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A new 
      butyrate releaser, useful for all the known applications of butyrate, presenting 
      physiochemical characteristics suitable for easy oral administration, 
      (N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA), has been recently developed. We 
      investigated the protective action of FBA against SARS-CoV-2 infection in the 
      human small intestine and enterocytes. Relevant aspects of SARS-CoV-2 infection 
      were assessed: infectivity, host functional receptor angiotensin-converting 
      enzyme-2 (ACE2), transmembrane protease serine 2 (TMPRSS2), neuropilin-1 (NRP1), 
      pro-inflammatory cytokines expression, genes involved in the antiviral response 
      and the activation of Nf-kB nuclear factor (erythroid-derived 2-like) 2 (Nfr2) 
      pathways. We found that FBA positively modulates the crucial aspects of the 
      infection in small intestinal biopsies and human enterocytes, reducing the 
      expression of ACE2, TMPRSS2 and NRP1, pro-inflammatory cytokines interleukin 
      (IL)-15, monocyte chemoattractant protein-1 (MCP-1) and TNF-alpha, and regulating 
      several genes involved in antiviral pathways. FBA was also able to reduce the 
      number of SARS-CoV-2-infected cells, and ACE2, TMPRSS2 and NRP1 expression. 
      Lastly, through the inhibition of Nf-kB and the up-regulation of Nfr2, it was 
      also able to reduce the expression of pro-inflammatory cytokines IL-15, MCP-1 and 
      TNF-alpha in human enterocytes. The new butyrate releaser, FBA, exerts a preventive 
      action against SARS-CoV-2 infection. It could be considered as an innovative 
      strategy to limit COVID-19.
FAU - Paparo, Lorella
AU  - Paparo L
AUID- ORCID: 0000-0002-5562-1408
AD  - Dipartimento di Scienze Mediche Translazionali, Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
AD  - CEINGE-Advanced Biotechnologies s.c.ar.l., Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
FAU - Maglio, Maria Antonia
AU  - Maglio MA
AD  - Dipartimento di Scienze Mediche Translazionali, Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
FAU - Cortese, Maddalena
AU  - Cortese M
AD  - Dipartimento di Scienze Mediche Translazionali, Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
AD  - CEINGE-Advanced Biotechnologies s.c.ar.l., Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
FAU - Bruno, Cristina
AU  - Bruno C
AD  - Dipartimento di Scienze Mediche Translazionali, Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
AD  - CEINGE-Advanced Biotechnologies s.c.ar.l., Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
FAU - Capasso, Mario
AU  - Capasso M
AUID- ORCID: 0000-0003-3306-1259
AD  - CEINGE-Advanced Biotechnologies s.c.ar.l., Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
AD  - Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Universita 
      degli Studi di Napoli "Federico II", 80131 Napoli, Italy.
FAU - Punzo, Erika
AU  - Punzo E
AD  - Dipartimento di Scienze Mediche Translazionali, Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
AD  - CEINGE-Advanced Biotechnologies s.c.ar.l., Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
FAU - Ferrucci, Veronica
AU  - Ferrucci V
AD  - CEINGE-Advanced Biotechnologies s.c.ar.l., Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
AD  - Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Universita 
      degli Studi di Napoli "Federico II", 80131 Napoli, Italy.
FAU - Lasorsa, Vito Alessandro
AU  - Lasorsa VA
AUID- ORCID: 0000-0002-9552-7192
AD  - CEINGE-Advanced Biotechnologies s.c.ar.l., Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
FAU - Viscardi, Maurizio
AU  - Viscardi M
AD  - DAI Medicina di Laboratorio e Trasfusionale, AOU Azienda Ospedaliera, Universita 
      degli Studi di Napoli "Federico II", 80131 Napoli, Italy.
FAU - Fusco, Giovanna
AU  - Fusco G
AD  - DAI Medicina di Laboratorio e Trasfusionale, AOU Azienda Ospedaliera, Universita 
      degli Studi di Napoli "Federico II", 80131 Napoli, Italy.
FAU - Cerino, Pellegrino
AU  - Cerino P
AD  - DAI Medicina di Laboratorio e Trasfusionale, AOU Azienda Ospedaliera, Universita 
      degli Studi di Napoli "Federico II", 80131 Napoli, Italy.
FAU - Romano, Alessia
AU  - Romano A
AD  - CEINGE-Advanced Biotechnologies s.c.ar.l., Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
FAU - Troncone, Riccardo
AU  - Troncone R
AD  - Dipartimento di Scienze Mediche Translazionali, Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
FAU - Zollo, Massimo
AU  - Zollo M
AUID- ORCID: 0000-0002-0970-7243
AD  - CEINGE-Advanced Biotechnologies s.c.ar.l., Universita degli Studi di Napoli 
      "Federico II", 80131 Napoli, Italy.
AD  - Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Universita 
      degli Studi di Napoli "Federico II", 80131 Napoli, Italy.
AD  - DAI Medicina di Laboratorio e Trasfusionale, AOU Azienda Ospedaliera, Universita 
      degli Studi di Napoli "Federico II", 80131 Napoli, Italy.
LA  - eng
GR  - POR FESR 2014/2020/Regione Campania/
PT  - Journal Article
DEP - 20220127
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Antiviral Agents)
RN  - 0 (Butyrates)
RN  - 0 (N-(1-carbamoyl-2-phenyl-ethyl)butyramide)
SB  - IM
MH  - Antiviral Agents/pharmacology
MH  - Butyrates/metabolism/*pharmacology
MH  - COVID-19/metabolism
MH  - Caco-2 Cells
MH  - Enterocytes/drug effects/metabolism
MH  - Gene Expression/genetics
MH  - Gene Expression Regulation/genetics
MH  - Humans
MH  - Intestines/drug effects/metabolism
MH  - Male
MH  - SARS-CoV-2/drug effects/*metabolism/pathogenicity
MH  - *COVID-19 Drug Treatment
PMC - PMC8838168
OTO - NOTNLM
OT  - COVID-19
OT  - angiotensin-converting enzyme-2
OT  - intestinal models
OT  - transmembrane protease serine 2
OT  - viral infection
COIS- The authors have no other conflict of interests that are directly relevant to the 
      content of this manuscript, which remains their sole responsibility.
EDAT- 2022/02/16 06:00
MHDA- 2022/02/19 06:00
PMCR- 2022/01/27
CRDT- 2022/02/15 01:19
PHST- 2021/12/15 00:00 [received]
PHST- 2022/01/12 00:00 [revised]
PHST- 2022/01/25 00:00 [accepted]
PHST- 2022/02/15 01:19 [entrez]
PHST- 2022/02/16 06:00 [pubmed]
PHST- 2022/02/19 06:00 [medline]
PHST- 2022/01/27 00:00 [pmc-release]
AID - molecules27030862 [pii]
AID - molecules-27-00862 [pii]
AID - 10.3390/molecules27030862 [doi]
PST - epublish
SO  - Molecules. 2022 Jan 27;27(3):862. doi: 10.3390/molecules27030862.