Evaluation of Small Molecule Combinations against Respiratory Syncytial Virus In Vitro

Gao, Yuzhen; Cao, Jiyue; Xing, Pan; Altmeyer, Ralf; Zhang, Youming

doi:10.3390/molecules26092607

Cited by 10 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although susceptible rodents succumb rapidly to RVFV infection, future studies should explore the antiviral potency of small molecule fusion inhibitors in vivo. Alternatively, the concurrent use of a fusion inhibitor and a viral polymerase inhibitor could potentially result in additive or synergistic antiviral effects, as previously described [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Computer-Selected Antiviral Compounds: Assessing In Vitro Efficacies against Rift Valley Fever Virus

Alkan,

O’Brien,

Kenyon

et al. 2024

Viruses

View full text Add to dashboard Cite

Rift Valley fever is a zoonotic viral disease transmitted by mosquitoes, impacting both humans and livestock. Currently, there are no approved vaccines or antiviral treatments for humans. This study aimed to evaluate the in vitro efficacy of chemical compounds targeting the Gc fusion mechanism. These compounds were identified through virtual screening of millions of commercially available small molecules using a structure-based artificial intelligence bioactivity predictor. In our experiments, a pretreatment with small molecule compounds revealed that 3 out of 94 selected compounds effectively inhibited the replication of the Rift Valley fever virus MP-12 strain in Vero cells. As anticipated, these compounds did not impede viral RNA replication when administered three hours after infection. However, significant inhibition of viral RNA replication occurred upon viral entry when cells were pretreated with these small molecules. Furthermore, these compounds exhibited significant inhibition against Arumowot virus, another phlebovirus, while showing no antiviral effects on tick-borne bandaviruses. Our study validates AI-based virtual high throughput screening as a rational approach for identifying effective antiviral candidates for Rift Valley fever virus and other bunyaviruses.

show abstract

Section: Discussionmentioning

confidence: 99%

Computer-Selected Antiviral Compounds: Assessing In Vitro Efficacies against Rift Valley Fever Virus

Alkan,

O’Brien,

Kenyon

et al. 2024

Viruses

View full text Add to dashboard Cite

show abstract

“…In this context, working with small molecules appears to be more promising. For example, the compound BMC-433771, developed by Bristol Myers Squibb selectively inhibits the F protein and has demonstrated activity in animal models [ 9 ], albeit in a prophylactic treatment regimen. Its derivative, Rilematovir (JNJ-53718678), is currently undergoing clinical trials [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus

Shtro,

Klabukov,

Garshinina

et al. 2023

IJMS

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) is known to cause annual epidemics of respiratory infections; however, the lack of specific treatment options for this disease poses a challenge. In light of this, there has been a concerted effort to identify small molecules that can effectively combat RSV. This article focuses on the mechanism of action of compound K142, which was identified as a primary screening leader in the earlier stages of the project. The research conducted demonstrates that K142 significantly reduces the intensity of virus penetration into the cells, as well as the formation of syncytia from infected cells. These findings show that the compound’s interaction with the surface proteins of RSV is a key factor in its antiviral activity. Furthermore, pharmacological modeling supports that K142 effectively interacts with the F-protein. However, in vivo studies have shown only weak antiviral activity against RSV infection, with a slight decrease in viral load observed in lung tissues. As a result, there is a need to enhance the bioavailability or antiviral properties of this compound. Based on these findings, we hypothesize that further modifications of the compound under study could potentially increase its antiviral activity.

show abstract

“…Ziresovir is an RSV fusion inhibitor that reduces cytopathic effects in HEp-2 cell cultures [ 66 ] infected with both RSV A and B strains [ 67 ]. In a phase II study, AK0529 was well tolerated in hospitalized RSV-infected infant patients, and treatment with AK0529 2 mg/kg bid reduced viral load [ 68 ].…”

Section: Management and Preventionmentioning

confidence: 99%

Respiratory Syncytial Virus Infection in Older Adults: An Update

Alfano,

Bigoni,

Caggiano

et al. 2024

Drugs Aging

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) infection represents one of the most common infections during childhood, with significant morbidity and mortality in newborns and in the early years of life. RSV is a common infection throughout all age groups, largely undetected and underestimated in adults, with a disproportionately high impact in older individuals. RSV infection has a wide range of clinical presentations, from asymptomatic conditions to acute pneumonia and severe life-threatening respiratory distress, including exacerbations of underlying chronic conditions. Overall, the incidence of RSV infections requiring medical attention increases with age, and it is highest among persons ≥ 70 years of age. As a consequence of a combination of an aging population, immunosenescence, and the related increased burden of comorbidities, high-income countries are at risk of developing RSV epidemics. The standard of care for RSV-infected patients remains supportive, including fluids, antipyretics, and oxygen support when needed. There is an urgent need for antivirals and preventive strategies in this population, particularly in individuals at higher risk of severe outcomes following RSV infection. In this review, we describe prevention and treatment strategies for RSV illnesses, with a deep focus on the novel data on vaccination that has become available (Arexvy, GSK, and Abrysvo, Pfizer) for older adults.

show abstract

Evaluation of Small Molecule Combinations against Respiratory Syncytial Virus In Vitro

Cited by 10 publications

References 43 publications

Computer-Selected Antiviral Compounds: Assessing In Vitro Efficacies against Rift Valley Fever Virus

Computer-Selected Antiviral Compounds: Assessing In Vitro Efficacies against Rift Valley Fever Virus

Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus

Respiratory Syncytial Virus Infection in Older Adults: An Update

Contact Info

Product

Resources

About