MBZM-N-IBT, a Novel Small Molecule, Restricts Chikungunya Virus Infection by Targeting nsP2 Protease Activity
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De, Saikat; Ghosh, Soumyajit; Keshry, Supriya Suman; Mahish, Chandan; Mohapatra, Chinmayee; Guru, Ankeeta; Mamidi, Prabhudutta; Datey, Ankita; Pani, Sweta Smita; Vasudevan, D.; Beuria, Tushar Kant; Chattopadhyay, Subhasis; Subudhi, Bharat Bhusan; Chattopadhyay, Soma

doi:10.1128/aac.00463-22

Cited by 7 publications

(5 citation statements)

References 60 publications

(87 reference statements)

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“…The IC 50 of DDABT1 was found to be 21.07 and 14.59 μM for 0.1 and 0.01 MOI, respectively (Figure D). Hence, the result indicates that DDABT1 inhibits CHIKV infection more efficiently than TM …”

Section: Resultsmentioning

confidence: 91%

“…For the post-treatment assay, cells were infected with CHIKV-PS for 1.5 h, washed three times with 1× PBS, and then incubated with DDABT1 containing DMEM medium. In all three cases, the cells and supernatants were harvested at 18 hpi for assessing the expressions of viral RNA by qRT-PCR, viral structural and nonstructural proteins by Western blot, and viral titer by the plaque assay …”

Section: Methodsmentioning

confidence: 99%

“…Confluent Vero cells (90% confluency) seeded in 35 mm cell culture dishes (TPP, Trasachingen, Switzerland) were infected with CHIKV (PS strain) with a multiplicity of infection (MOI 0.1). , Infection was performed for 90 min. Then the plates were washed thrice with 1× PBS and fresh complete media (DMEM) was added.…”

Section: Methodsmentioning

confidence: 99%

“…Then, coverslips were mounted with an antifade (Invitrogen). Fluorescence microscopic images were acquired using the Leica TCS SP5 confocal microscope (Leica Microsystems, Heidelberg, Germany) using a 20× objective, and images were analyzed using the Leica application suite (LASX) software …”

Section: Methodsmentioning

confidence: 99%

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Salicylic Acid Conjugate of Telmisartan Inhibits Chikungunya Virus Infection and Inflammation

Dash,

Ray,

Mamidi

et al. 2023

ACS Omega

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There is no approved antiviral for the management of the Chikungunya virus (CHIKV). To develop an antiviral drug that can manage both CHIKV and arthritis induced by it, an ester conjugate of telmisartan (TM) and salicylic acid (SA) was synthesized (DDABT1). It showed higher potency (IC50 of 14.53 μM) and a good selectivity index [(SI = CC50/IC50) > 33]. On post-treatment of DDABT1, CHIKV infection was inhibited significantly by reducing CPE, viral titer, viral RNA, and viral proteins. Further, the time of addition experiment revealed >95% inhibition up to 4hpi indicating its interference predominantly in the early stages of infection. However, the late stages were also affected. This conjugate of SA and TM was found to increase the antiviral efficacy, and this might be partly attributed to modulating angiotensin II (Ang II) receptor type 1 (AT1). However, DDABT1 might have other modes of action that need further investigation. In addition, the in vivo experiments showed an LD50 of 5000 mg/kg in rats and was found to be more effective than TM, SA, or their combination against acute, subacute, and chronic inflammation/arthritis in vivo. In conclusion, DDABT1 showed remarkable anti-CHIKV properties and the ability to reduce inflammation and arthritis, making it a very good potential drug candidate that needs further experimental validation.

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Section: Resultsmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Salicylic Acid Conjugate of Telmisartan Inhibits Chikungunya Virus Infection and Inflammation

Dash,

Ray,

Mamidi

et al. 2023

ACS Omega

Self Cite

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“…Bin Zou and colleagues ( 133 ) used a viral infection model in mice with DENV and observed a reduction in viremia in the treated mice after oral administration of the drug. Another isatin derivative, 1-[(2-methylbenzimidazol-1-yl)methyl]-2-oxo-indolin-3-ylidene]-amino]thiourea (MBZM-N-IBT), demonstrated antiviral activity against CHIKV by inhibiting the nsP2 protease activity in vitro and in vivo experiments ( 134 , 135 ).…”

Section: Outlook On Control Strategies Developmentmentioning

confidence: 99%

Integrated control strategies for dengue, Zika, and Chikungunya virus infections

Côrtes,

Lira,

Prates-Syed

et al. 2023

Front. Immunol.

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Arboviruses are a major threat to public health in tropical regions, encompassing over 534 distinct species, with 134 capable of causing diseases in humans. These viruses are transmitted through arthropod vectors that cause symptoms such as fever, headache, joint pains, and rash, in addition to more serious cases that can lead to death. Among the arboviruses, dengue virus stands out as the most prevalent, annually affecting approximately 16.2 million individuals solely in the Americas. Furthermore, the re-emergence of the Zika virus and the recurrent outbreaks of chikungunya in Africa, Asia, Europe, and the Americas, with one million cases reported annually, underscore the urgency of addressing this public health challenge. In this manuscript we discuss the epidemiology, viral structure, pathogenicity and integrated control strategies to combat arboviruses, and the most used tools, such as vaccines, monoclonal antibodies, treatment, etc., in addition to presenting future perspectives for the control of arboviruses. Currently, specific medications for treating arbovirus infections are lacking, and symptom management remains the primary approach. However, promising advancements have been made in certain treatments, such as Chloroquine, Niclosamide, and Isatin derivatives, which have demonstrated notable antiviral properties against these arboviruses in vitro and in vivo experiments. Additionally, various strategies within vector control approaches have shown significant promise in reducing arbovirus transmission rates. These encompass public education initiatives, targeted insecticide applications, and innovative approaches like manipulating mosquito bacterial symbionts, such as Wolbachia. In conclusion, combatting the global threat of arbovirus diseases needs a comprehensive approach integrating antiviral research, vaccination, and vector control. The continued efforts of research communities, alongside collaborative partnerships with public health authorities, are imperative to effectively address and mitigate the impact of these arboviral infections on public health worldwide.

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Conjugates of ibuprofen inhibit CHIKV infection and inflammation

Dash

Mamidi

et al. 2023

Mol Divers

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MBZM-N-IBT, a Novel Small Molecule, Restricts Chikungunya Virus Infection by Targeting nsP2 Protease Activity In Vitro , In Vivo , and Ex Vivo

Abstract: The increase in disease incidences and persistent Chikungunya virus (CHIKV)-induced arthritis have been a huge burden on public health globally. In the absence of specific antivirals or vaccines, it is essential to continue efforts to develop effective anti-CHIKV strategies.

Cited by 7 publications

References 60 publications

Salicylic Acid Conjugate of Telmisartan Inhibits Chikungunya Virus Infection and Inflammation

Salicylic Acid Conjugate of Telmisartan Inhibits Chikungunya Virus Infection and Inflammation

Integrated control strategies for dengue, Zika, and Chikungunya virus infections

Conjugates of ibuprofen inhibit CHIKV infection and inflammation

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