Respiratory syncytial virus (RSV) is a single-stranded, negative-strand, non-segmented RNA virus belonging to the family Paramyxoviridae and the genus Pneumovirus.
Infection with this virus often causes bronchiolitis and pneumonia in infants under 6 months of age.
Other respiratory diseases, older children and adults can be infected with symptoms such as rhinitis and colds, and RSV infection in the elderly can lead to serious complications, such as chronic obstructive pulmonary disease and congestive heart failure
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Ribavirin is the only small-molecule drug approved by the FDA for the treatment of RSV infection.
However, the use of ribavirin has many side effects, and there is insufficient clinical evidence to confirm its role in the treatment of RSV infection.
Effective, it is not recommended for routine use
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Because it is an urgently needed product in clinical practice, many domestic and foreign pharmaceutical companies have launched anti-RSV drug research and development.
Pfizer recently announced that it plans to spend US$525 million to acquire ReViral, which focuses on the research and development of new anti-RSV therapies
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On April 16, 2022, Signal Transduction and Targeted Therapy published online a question completed by the team of Xiao Gengfu / Zhang Leiping from Wuhan Institute of Virology/State Key Laboratory of Virology, Chinese Academy of Sciences and the team of Shen Jingshan / Xie Yuanchao from Shanghai Institute of Materia Medica, Chinese Academy of Sciences .
This is the study of Oral remdesivir derivative VV116 is a potent inhibitor of respiratory syncytial virus with efficacy in a mouse model
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The study found that the oral nucleoside anti-new coronavirus drug VV116 has excellent antiviral effect on multiple sensitive cell lines of RSV.
In the mouse model, VV116 has high oral bioavailability, good tissue distribution and significant advantages.
The antiviral effect of ribavirin, and can alleviate the pathological damage of lung tissue
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This study provides a valuable clinical candidate for the treatment of RSV infection
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In this study, the antiviral effects of 6 nucleoside analogs, including remdesivir nucleoside (GS-441524), remdesivir (RDV), and reported RSV inhibition, were first explored on 3 RSV-sensitive cell lines.
ALS-8112, VV116 nucleoside (X1), VV116 base (X6) and VV116
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The structures of the compounds are shown in Figure 1a, and the antiviral effects of these compounds on human alveolar basal epithelial cancer cells (A549) are shown in Figure 1b
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The Balb/c mouse model was further used to explore the concentration of nucleoside metabolite X1 in the blood of mice after a single oral dose of VV116 25 mg/kg, 50 mg/kg and 100 mg/kg (Fig.
1c) , as well as a single oral dose of VV116.
Concentrations of X1 in liver, lung and blood after 100 mg/kg (Fig.
1d)
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Combined with the results of cell-level antiviral and animal-level drug metabolism studies, the Balb/c mouse model was used to explore the antiviral effect of VV116 at the animal level, considering that the Balb/c mouse model reached viral replication on the 4th day of RSV infection At the peak period, mice were euthanized on the 4th day after challenge, and lung tissue was collected to detect viral load (Fig.
1e) , virus titer (Fig.
1e), and lung pathology (Fig.
1f)
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Figure 1.
Text Results Graph
At present, there are no preventive RSV vaccines and small-molecule specific drugs for the treatment of RSV infection
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The above in vivo efficacy studies provide strong evidence for the potential therapeutic effect of VV116 on RSV infection, which will be validated in later clinical studies
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VV116 demonstrated favorable safety, tolerability and pharmacokinetic properties in healthy subjects, and the results of three Phase I clinical trials were published online in the journal Acta Pharmacologica Sinica in March
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The results of a clinical study conducted in Uzbekistan in 2021 showed that compared with the control group, the VV116 group could better improve the clinical symptoms of patients, shorten the time to negative for the new coronavirus nucleic acid, and significantly reduce the risk of progression to critical illness and death
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VV116 has been approved for clinical use in Uzbekistan in 2021 as an oral anti-coronavirus
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Zhang Ruxue , post-doctoral researcher of Wuhan Institute of Virology, Chinese Academy of Sciences , and Zheng Wei , doctoral student of Shanghai Institute of Materia Medica are the co-first authors.
Researcher Xie Yuanchao of Lingang Laboratory and researcher Zhang Leiping of Wuhan Institute of Virology, Chinese Academy of Sciences are co-corresponding authors
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