Is the anti-psychotic, 10-(3-(dimethylamino)propyl)phenothiazine (promazine), a potential drug with which to treat SARS infections?

Barnard, Dale L.; Day, Craig W.; Bailey, Kevin W.; Heiner, Matthew; Montgomery, Robert A.; Lauridsen, Larry; Jung, Kie Hoon; Li, Joseph K.-K.; Chan, Paul K.S.; Sidwell, Robert W.

doi:10.1016/j.antiviral.2007.12.005

Cited by 17 publications

(19 citation statements)

References 20 publications

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“…In vitro data confirmed recent findings by Barnard et al (Barnard et al, 2008; Barnard et al, 2006b) that promazine, an antipsychotic drug, and ribavirin, a nucleoside analog, were not effective against SARS-CoV in vitro. Findings with v2163 supported prior findings that Infergen™ was active in vitro against SARS-CoV Urbani (Kumaki et al, 2008).…”

Section: Discussionsupporting

confidence: 88%

A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo

Day

Baric

Cai³

et al. 2009

Virology

Self Cite

133

168

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Severe acute respiratory syndrome (SARS) is a highly lethal emerging disease caused by coronavirus SARS-CoV. New lethal animal models for SARS were needed to facilitate antiviral research. We adapted and characterized a new strain of SARS-CoV (strain v2163) that was highly lethal in 5–6 week old BALB/c mice. It had nine mutations affecting 10 amino acid residues. Strain v2163 increased IL-1α, IL-6, MIP-1α, MCP-1, and RANTES in mice, and high IL-6 expression correlated with mortality. The infection largely mimicked human disease, but lung pathology lacked hyaline membrane formation. In vitro efficacy against v2163 was shown with known inhihibitors of SARS-CoV replication. In v2163-infected mice, Ampligen™ was fully protective, stinging nettle lectin (UDA) was partially protective, ribavirin was disputable and possibly exacerbated disease, and EP128533 was inactive. Ribavirin, UDA and Ampligen™ decreased IL-6 expression. Strain v2163 provided a valuable model for anti-SARS research.

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Section: Discussionsupporting

confidence: 88%

A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo

Day

Baric

Cai³

et al. 2009

Virology

Self Cite

133

168

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“…Although, several reports delineated the efficacy of certain NSMIs viz., ribavirin, promazine , and IMP dehydrogenase inhibitors to inhibit in vivo models of SARS- CoV replication, later, they were proven ineffective ( 60 , 150 – 152 ). A report by Reghunathan et al ( 153 ) showed that the immune response produced against SARS-CoV may be different from other viral infections as indicated by the lack of upregulation in MHC-I genes, cytokines, and IFNs or complement-mediated cytolysis in peripheral blood mononuclear cells (PBMCs).…”

Section: Introductionmentioning

confidence: 99%

Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status

et al. 2020

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Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease-19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. The clinical manifestations of this disease are pneumonia, lung injury, inflammation, and severe acute respiratory syndrome (SARS). Currently, there is no vaccine or effective pharmacological agents available for the prevention/treatment of SARS-CoV2 infections. Moreover, development of a suitable vaccine is a challenging task due to antibody-dependent enhancement (ADE) and Th-2 immunopathology, which aggravates infection with SARS-CoV-2. Furthermore, the emerging SARS-CoV-2 strain exhibits several distinct genomic and structural patterns compared to other coronavirus strains, making the development of a suitable vaccine even more difficult. Therefore, the identification of novel small molecule inhibitors (NSMIs) that can interfere with viral entry or viral propagation is of special interest and is vital in managing already infected cases. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, the development of novel inhibitors of ACE2/TMPRSS2 is likely to be beneficial in combating SARS-CoV-2 infections. However, the usage of ACE-2 inhibitors to block the SARS-CoV-2 viral entry requires additional studies as there are conflicting findings and severe health complications reported for these inhibitors in patients. Hence, the current interest is shifted toward the development of NSMIs, which includes natural antiviral phytochemicals Beeraka et al. Strategies for Targeting SARS-CoV-2: NSMIs and Nrf-2 activators to manage a SARS-CoV-2 infection. It is imperative to investigate the efficacy of existing antiviral phytochemicals and Nrf-2 activators to mitigate the SARS-CoV-2-mediated oxidative stress. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs.

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“…A total of six studies were included in scoping review and meta-analysis [19][20][21][22][23][24]. All studies originated from the United States of America (USA) and utilized mice and marmosets, but only the analyses with mice are taken into consideration.…”

Section: Characteristics Features Of the Included Studiesmentioning

confidence: 99%

“…The coronavirus disease that originated in 2019 (also referred to as COVID- 19) is an emerging infectious disease that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The global pandemic disease which sprung forth from Wuhan City, in Hubei Province of China was rst reported by the World Health Organization (WHO) on 31 December 2019.…”

Section: Introductionmentioning

confidence: 99%

Identification of SARS-CoV-2 preclinical (in vivo) compounds targeting COVID-19 main protease: A scoping review, meta-analysis and molecular docking studies

Ebenezer

Jordaan

Damoyi

et al. 2020

Preprint

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Due to the migratory flow of infected people with severe acute respiratory syndrome virus (SARS-CoV-2), the numbers of confirmed cases of coronavirus 2019 (COVID-19) infections is accelerating worldwide and pre-clinical evidence of antiviral agents that can combat this pandemic is still elusive. We identified published SAR-CoV efficacy experiments in which some selected compounds were used to test the reduction of the virus load in mice. We then developed a combined model based on scoping review, meta-analyses, and molecular docking studies to evaluate the effect size of preclinical studies of compounds that have been tested against SARS-CoV. Molecular docking studies of the inhibitors in the active pocket of COVID-19 protease were also performed. Our results identified three SARS-CoV inhibitors i.e. EIDD-2801, GS-5734 and amodiaquine that are excellent options for optimization and drug development to treat or cure COVID-19.

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Is the anti-psychotic, 10-(3-(dimethylamino)propyl)phenothiazine (promazine), a potential drug with which to treat SARS infections?

Cited by 17 publications

References 20 publications

A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo

A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo

Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status

Identification of SARS-CoV-2 preclinical (in vivo) compounds targeting COVID-19 main protease: A scoping review, meta-analysis and molecular docking studies

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