Mycophenolic acid (MPA) modulates host cellular autophagy progression in sub genomic dengue virus-2 replicon cells

Manchala, Nageswar Reddy; Dungdung, Ranjeet; Trivedi, Pankaj; Unniyampurath, Unnikrishnan; Pilankatta, Rajendra

doi:10.1016/j.micpath.2019.103762

Cited by 7 publications

(6 citation statements)

References 29 publications

(29 reference statements)

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“…Regarding mycophenolate mofetil (MMF) and mycophenolic acid (MPA), MMF is a prodrug of MPA and both of them are immunosuppressants used to prevent rejection of transplant [ 18 ]. MMF and MPA have been reported to have antiviral activity against Hepatitis C Virus (HCV), human herpes virus, DENV, and SARS-CoV-2 [ 19 , 20 , 21 , 22 ]. We found that the addition of gemcitabine, MMF, and MPA could significantly inhibit SADS-CoV infection and replication, especially by inhibiting the post-entry stages ( Figure 4 C–E).…”

Section: Resultsmentioning

confidence: 99%

Antiviral Drugs Screening for Swine Acute Diarrhea Syndrome Coronavirus

Chen

You

Wang

et al. 2022

IJMS

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Coronaviruses as possible cross-species viruses have caused several epidemics. The ongoing emergency of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed severe threats to the global economy and public health, which has generated great concerns about zoonotic viruses. Swine acute diarrhea syndrome coronavirus (SADS-CoV), an alpha-coronavirus, was responsible for mass piglet deaths, resulting in unprecedented economic losses, and no approved drugs or vaccines are currently available for SADS-CoV infection. Given its potential ability to cause cross-species infection, it is essential to develop specific antiviral drugs and vaccines against SADS-CoV. Drug screening was performed on a total of 3523 compound-containing drug libraries as a strategy of existing medications repurposing. We identified five compounds (gemcitabine, mycophenolate mofetil, mycophenolic acid, methylene blue and cepharanthine) exhibiting inhibitory effects against SADS-CoV in a dose-dependent manner. Cepharanthine and methylene blue were confirmed to block viral entry, and gemcitabine, mycophenolate mofetil, mycophenolic acid and methylene blue could inhibit viral replication after SADS-CoV entry. This is the first report on SADS-CoV drug screening, and we found five compounds from drug libraries to be potential anti-SADS-CoV drugs, supporting the development of antiviral drugs for a possible outbreak of SADS-CoV in the future.

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Section: Resultsmentioning

confidence: 99%

Antiviral Drugs Screening for Swine Acute Diarrhea Syndrome Coronavirus

Chen

You

Wang

et al. 2022

IJMS

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“…CSJD may inhibit the occurrence of autophagy by down-regulating the expression of AKT1 by targeting, thus hindering the replication of dengue virus. [ 39 ] STAT3 is a key transcription factor mediating the early response of dengue shock syndrome. Relevant studies have suggested that the decrease of STAT3 level can lead to a significant decrease in the expression and replication of dengue virus protein, and CSJD may inhibit the expression and replication of Dengue virus by reducing the level of STAT3 in patients.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanism of ChaiShi JieDu granule in treating dengue based on network pharmacology and molecular docking: A review

Li,

Lin,

Tang

et al. 2023

Medicine

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Dengue fever is a frequently occurring infectious disease caused by the Dengue virus, prevalent in tropical and subtropical regions. Chaishi Jiedu Granules (CSJD) is an empirical prescription of the Eighth Affiliated Hospital of Guangzhou Medical University in the treatment of dengue fever, which has been widely used in the treatment of dengue fever, and has shown good efficacy in improving the clinical symptoms of patients. This study aims to explore the molecular mechanism of CSJD in treating dengue fever using network pharmacology, molecular docking techniques, and virtual screening methods. The results showed that luteolin, quercetin and other compounds in CSJD could target important targets related to dengue virus, including STAT3, AKT1, TNF, IL-6, and other key genes, thus playing an antiviral role. Among them, luteolin and wogonin in CSJD also inhibited dengue virus replication and reduced inflammation, and showed good binding force with IL-6 and TNF. Therefore, this study provides an important reference for the development of CSJD as a potential drug for dengue fever treatment and a new perspective for research and development in this field.

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“…Mycophenolic acid is commonly used for the prevention of rejection in kidney and liver transplantation and has been shown to inhibit flavivirus infection in mammalian cells by preventing the synthesis and accumulation of viral RNA, to suppress DENV2 infection in mosquito midguts and dissemination to salivary glands when administered through a blood or sugar meal, and to inhibit ZIKV infection in both mosquito cells and adults [ 41 , 42 ]. In addition, Mycophenolic acid has been documented to have antiviral activity against many viruses ( Table 7 ) [ 17 , 43 , 44 , 45 , 46 , 47 ]. Mycophenolic acid has previously been shown to exhibit anti-ZIKV activity in Vero cells infected with ZIKV SL1602 strain (EC 50 of 0.42 µM); in Huh7, HeLa and HAEC cells infected with ZIKV MEX_I_7 strain (EC 50 < 2 µM); in U2OS cells infected with ZIKV MEX-2-81 strain (EC 50 of 0.4 µM); and in JEG-3 and HBME cells infected with a ZIKV cocktail of MR-766, FSS13025, and MEX-2-81 strains (EC 50 of 0.1 µM) and inhibitory effects were described in Vero cells infected with ZIKV MR-766 (EC 50 of 0.11) and PRVABC59 (EC 50 0.14 µM) [ 24 , 34 , 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Inhibitors of ZIKV Replication

Vasquez

Park

Ávila‐Pérez

et al. 2020

Viruses

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Zika virus (ZIKV) was identified in 1947 in the Zika forest of Uganda and it has emerged recently as a global health threat, with recurring outbreaks and its associations with congenital microcephaly through maternal fetal transmission and Guillain-Barré syndrome. Currently, there are no United States (US) Food and Drug Administration (FDA)-approved vaccines or antivirals to treat ZIKV infections, which underscores an urgent medical need for the development of disease intervention strategies to treat ZIKV infection and associated disease. Drug repurposing offers various advantages over developing an entirely new drug by significantly reducing the timeline and resources required to advance a candidate antiviral into the clinic. Screening the ReFRAME library, we identified ten compounds with antiviral activity against the prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV). Moreover, we showed the ability of these ten compounds to inhibit influenza A and B virus infections, supporting their broad-spectrum antiviral activity. In this study, we further evaluated the broad-spectrum antiviral activity of the ten identified compounds by testing their activity against ZIKV. Among the ten compounds, Azaribine (SI-MTT = 146.29), AVN-944 (SI-MTT = 278.16), and Brequinar (SI-MTT = 157.42) showed potent anti-ZIKV activity in post-treatment therapeutic conditions. We also observed potent anti-ZIKV activity for Mycophenolate mofetil (SI-MTT = 20.51), Mycophenolic acid (SI-MTT = 36.33), and AVN-944 (SI-MTT = 24.51) in pre-treatment prophylactic conditions and potent co-treatment inhibitory activity for Obatoclax (SI-MTT = 60.58), Azaribine (SI-MTT = 91.51), and Mycophenolate mofetil (SI-MTT = 73.26) in co-treatment conditions. Importantly, the inhibitory effect of these compounds was strain independent, as they similarly inhibited ZIKV strains from both African and Asian/American lineages. Our results support the broad-spectrum antiviral activity of these ten compounds and suggest their use for the development of antiviral treatment options of ZIKV infection.

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Mycophenolic acid (MPA) modulates host cellular autophagy progression in sub genomic dengue virus-2 replicon cells

Cited by 7 publications

References 29 publications

Antiviral Drugs Screening for Swine Acute Diarrhea Syndrome Coronavirus

Antiviral Drugs Screening for Swine Acute Diarrhea Syndrome Coronavirus

Molecular mechanism of ChaiShi JieDu granule in treating dengue based on network pharmacology and molecular docking: A review

Identification of Inhibitors of ZIKV Replication

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