PMID- 32313883
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2632-2919 (Electronic)
IS  - 2632-2900 (Print)
IS  - 2632-2900 (Linking)
VI  - 2
IP  - 3
DP  - 2020 May
TI  - Inhaled biguanides and mTOR inhibition for influenza and coronavirus (Review).
LID - 1 [pii]
LID - 10.3892/wasj.2020.42 [doi]
AB  - The mammalian target of rapamycin (mTOR) signaling pathway senses and responds to 
      nutrient availability, energy sufficiency, stress, hormones and mitogens to 
      modulate protein synthesis. Rapamycin is a bacterial product that can inhibit 
      mTOR via the PI3K/AKT/mTOR pathway. mTOR signaling is necessary for the 
      development of influenza and modulates the antibody response to provide 
      cross-protective immunity to lethal infection with influenza virus. In one human 
      study, it was found that the treatment of severe H1N1 influenza‑related pneumonia 
      with rapamycin and steroids improved the outcome. However, in other studies, 
      immunosuppression with systemic steroids, and possibly rapamycin as well, was 
      associated with an increased morbidity/mortality and a prolonged viral 
      replication. In order to avoid the systemic side-effects, some investigators have 
      postulated that the inhalation of rapamycin would be desirable. However, the 
      inhalation of rapamycin, with its well-documented lung toxicity, could be 
      contraindicated. Another class of drug, biguanides, can also inhibit mTOR, but 
      have no lung toxicity. Biguanides are widely used small molecule drugs prescribed 
      as oral anti-diabetics that have exhibited considerable promise in oncology. 
      During the 1971 outbreak of influenza, diabetic patients treated with the 
      biguanides, phenformin and buformin, had a lower incidence of infection than 
      diabetics treated with sulfonylureas or insulin. Both buformin and phenformin 
      reduce the mortality of influenza in mice; phenformin is less effective than 
      buformin. The inhalation of buformin or phenformin for influenza may be an 
      effective novel treatment strategy that would limit the risk of systemic 
      side-effects associated with biguanides due to the low inhaled dose. Coronavirus 
      disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2, a virus 
      closely related to the SARS virus. The disease is the cause of the 2019-2020 
      coronavirus outbreak. It is primarily spread between individuals via small 
      droplets emitted from infected individuals when breathing or coughing. 
      PI3K/AKT/mTOR signaling responses play important roles in MERS-CoV infection and 
      may represent a novel drug target for therapeutic intervention strategies. The 
      present review article discusses the effects of biguanides on influenza and 
      coronavirus.
FAU - Lehrer, Steven
AU  - Lehrer S
AD  - Fermata Pharma Inc., New York, NY 10023-7909, USA.
LA  - eng
GR  - R01 CA049506/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20200329
PL  - England
TA  - World Acad Sci J
JT  - World Academy of Sciences journal
JID - 101760660
PMC - PMC7170270
MID - NIHMS1579720
OTO - NOTNLM
OT  - biguanides
OT  - buformin
OT  - influenza
OT  - inhaled
OT  - mammalian target of rapamycin
COIS- Competing interests The authors declare that they have no competing interests.
EDAT- 2020/04/22 06:00
MHDA- 2020/04/22 06:01
PMCR- 2020/05/01
CRDT- 2020/04/22 06:00
PHST- 2020/04/22 06:00 [entrez]
PHST- 2020/04/22 06:00 [pubmed]
PHST- 2020/04/22 06:01 [medline]
PHST- 2020/05/01 00:00 [pmc-release]
AID - 1 [pii]
AID - 10.3892/wasj.2020.42 [doi]
PST - ppublish
SO  - World Acad Sci J. 2020 May;2(3):1. doi: 10.3892/wasj.2020.42. Epub 2020 Mar 29.