Abstract: Medicine
®
Systematic Review and Meta-Analysis
The safety and efficacy of oral antiviral drug
VV116 for treatment of COVID-19
wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 01/29/2024
A systematic review
Ningkun Xiao, MDa,* , Xinlin Huang, MDa, Xiaotian Kang, Bachelorb, Wanli Zang, MDc, Bo Li, MDd,
Sergey Kiselev, PhDa
Abstract
Background: Recent trials have highlighted the potential of oral antiviral VV116 in the treatment of patients with mild COVID-
19. However, no comprehensive studies have assessed the safety and efficacy of VV116. Therefore, we conducted a systematic
review to assess the safety and efficacy of VV116.
Methods: A comprehensive search was conducted on PubMed, Scopus, and Google Scholar websites, with a cutoff date of
March 23, to identify pertinent studies.
Results: The results from the 3 included studies indicated that no serious adverse events were reported in the VV116 experimental
groups, which exhibited a 2.57-day faster time to viral shedding than the control group and demonstrated non-inferiority to the
nirmatrelvir-ritonavir control group in alleviating major symptoms.
Discussion: Collectively, available studies suggest a reliable safety and efficacy profile for VV116. However, the limited number
of trials was insufficient for meta-analysis, and the included population consisted of younger individuals with mild and moderate
symptoms, not encompassing the elderly who are severely affected by COVID-19. We hope that more studies will be conducted
in the future to ensure that VV116 has a more reliable safety and efficacy profile in the clinical setting, especially in severe or critical
patients.
Abbreviations: AEs = adverse events, AUC = concentration-time curve, Cmax = the maximum measured plasma concentration,
COVID-19 = corona virus disease 2019, NR = nirmatrelvir/ritonavir, PEDro = Physiotherapy Evidence Database scale, SARSCoV-2 = severe acute respiratory syndrome coronavirus 2.
Keywords: COVID-19, oral antiviral drug, public health, vaccines, VV116
have high spike protein mutation rates. There is a higher probability of vaccine breakthrough rates and widespread escape
from existing neutralizing antibodies,[8,9] more specifically, The
BQ and XBB subvariants of SARS-CoV-2 Omicron are currently
expanding rapidly, and BQ.1, BQ.1.1, XBB, and XBB.1 are the
most resistant SARS-CoV-2 variations to date,[10] which poses
a huge challenge to the immune protection of the majority of
the population and a threat to worldwide health endeavors.
Consequently, adjunct medications have become increasingly
important for safeguarding global health.
The U.S. Food and Drug Administration has approved 2 oral
antiviral drugs for the treatment of mild to moderate COVID-19
outpatients at risk of progression to severe COVID-19: Pfizer’s
PF-07321332 (nirmatrelvir/ritonavir, paxlovid)[11,12] and Merck’s
DOI record:
{
"DOI": "10.1097/md.0000000000034105",
"ISSN": [
"0025-7974"
],
"URL": "http://dx.doi.org/10.1097/MD.0000000000034105",
"abstract": "<jats:sec><jats:title>Background:</jats:title><jats:p>Recent trials have highlighted the potential of oral antiviral VV116 in the treatment of patients with mild COVID-19. However, no comprehensive studies have assessed the safety and efficacy of VV116. Therefore, we conducted a systematic review to assess the safety and efficacy of VV116.</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>A comprehensive search was conducted on PubMed, Scopus, and Google Scholar websites, with a cutoff date of March 23, to identify pertinent studies.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>The results from the 3 included studies indicated that no serious adverse events were reported in the VV116 experimental groups, which exhibited a 2.57-day faster time to viral shedding than the control group and demonstrated non-inferiority to the nirmatrelvir-ritonavir control group in alleviating major symptoms.</jats:p></jats:sec><jats:sec><jats:title>Discussion:</jats:title><jats:p>Collectively, available studies suggest a reliable safety and efficacy profile for VV116. However, the limited number of trials was insufficient for meta-analysis, and the included population consisted of younger individuals with mild and moderate symptoms, not encompassing the elderly who are severely affected by COVID-19. We hope that more studies will be conducted in the future to ensure that VV116 has a more reliable safety and efficacy profile in the clinical setting, especially in severe or critical patients.</jats:p></jats:sec>",
"author": [
{
"ORCID": "http://orcid.org/0000-0002-0615-3222",
"affiliation": [
{
"name": "Laboratory for Brain and Neurocognitive Development, Department of Psychology, Institution of Humanities, Ural Federal University, Yekaterinburg, Russia"
}
],
"authenticated-orcid": false,
"family": "Xiao",
"given": "Ningkun",
"sequence": "first"
},
{
"affiliation": [
{
"name": "Laboratory for Brain and Neurocognitive Development, Department of Psychology, Institution of Humanities, Ural Federal University, Yekaterinburg, Russia"
}
],
"family": "Huang",
"given": "Xinlin",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Faculty of General Medicine, Ural State Medical University, Yekaterinburg, Russia"
}
],
"family": "Kang",
"given": "Xiaotian",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Postgraduate School, University of Harbin Sport, Harbin, China"
}
],
"family": "Zang",
"given": "Wanli",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Institution of Humanities, Ural Federal University, Yekaterinburg, Russia."
}
],
"family": "Li",
"given": "Bo",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Laboratory for Brain and Neurocognitive Development, Department of Psychology, Institution of Humanities, Ural Federal University, Yekaterinburg, Russia"
}
],
"family": "Kiselev",
"given": "Sergey",
"sequence": "additional"
}
],
"container-title": "Medicine",
"content-domain": {
"crossmark-restriction": false,
"domain": []
},
"created": {
"date-parts": [
[
2023,
7,
7
]
],
"date-time": "2023-07-07T12:06:09Z",
"timestamp": 1688731569000
},
"deposited": {
"date-parts": [
[
2023,
12,
16
]
],
"date-time": "2023-12-16T16:42:59Z",
"timestamp": 1702744979000
},
"indexed": {
"date-parts": [
[
2023,
12,
16
]
],
"date-time": "2023-12-16T17:15:19Z",
"timestamp": 1702746919724
},
"is-referenced-by-count": 1,
"issue": "27",
"issued": {
"date-parts": [
[
2023,
7,
7
]
]
},
"journal-issue": {
"issue": "27",
"published-print": {
"date-parts": [
[
2023
]
]
}
},
"language": "en",
"license": [
{
"URL": "http://creativecommons.org/licenses/by-nc/4.0/",
"content-version": "unspecified",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2023,
7,
7
]
],
"date-time": "2023-07-07T00:00:00Z",
"timestamp": 1688688000000
}
}
],
"link": [
{
"URL": "https://journals.lww.com/10.1097/MD.0000000000034105",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "276",
"original-title": [],
"page": "e34105",
"prefix": "10.1097",
"published": {
"date-parts": [
[
2023,
7,
7
]
]
},
"published-print": {
"date-parts": [
[
2023,
7,
7
]
]
},
"publisher": "Ovid Technologies (Wolters Kluwer Health)",
"reference": [
{
"DOI": "10.3389/fimmu.2022.1015355",
"article-title": "Oral GS-441524 derivatives: next-generation inhibitors of SARS-CoV-2 RNA-dependent RNA polymerase.",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "1015355",
"journal-title": "Front Immunol",
"key": "R1-20230802",
"volume": "13",
"year": "2022"
},
{
"DOI": "10.1001/jama.2021.8565",
"article-title": "Effect of 2 Inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults: a randomized clinical trial.",
"author": "Al Kaabi",
"doi-asserted-by": "crossref",
"first-page": "35",
"journal-title": "JAMA",
"key": "R2-20230802",
"volume": "326",
"year": "2021"
},
{
"DOI": "10.1056/NEJMoa2116063",
"article-title": "Covid-19 Vaccine effectiveness in New York State.",
"author": "Rosenberg",
"doi-asserted-by": "crossref",
"first-page": "116",
"journal-title": "N Engl J Med",
"key": "R3-20230802",
"volume": "386",
"year": "2021"
},
{
"DOI": "10.1038/s41423-022-00890-1",
"article-title": "Neutralizing antibodies and their cocktails against SARS-CoV-2 Omicron and other circulating variants.",
"author": "Yang",
"doi-asserted-by": "crossref",
"first-page": "962",
"journal-title": "Cell Mol Immunol",
"key": "R4-20230802",
"volume": "19",
"year": "2022"
},
{
"DOI": "10.1016/j.scib.2022.02.011",
"article-title": "COVID-19 can be called a treatable disease only after we have antivirals.",
"author": "Zhang",
"doi-asserted-by": "crossref",
"first-page": "999",
"journal-title": "Sci Bull (Beijing)",
"key": "R5-20230802",
"volume": "67",
"year": "2022"
},
{
"DOI": "10.1080/22221751.2022.2078230",
"article-title": "An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants.",
"author": "Shen",
"doi-asserted-by": "crossref",
"first-page": "1518",
"journal-title": "Emerg Microbes Infect",
"key": "R6-20230802",
"volume": "11",
"year": "2022"
},
{
"DOI": "10.1002/iid3.733",
"article-title": "Emergence of SARS-CoV-2 Omicron variant and strategies for tackling the infection.",
"author": "Wu",
"doi-asserted-by": "crossref",
"first-page": "e733",
"journal-title": "Immun Inflammation Dis",
"key": "R7-20230802",
"volume": "10",
"year": "2022"
},
{
"DOI": "10.1016/j.cell.2021.12.046",
"article-title": "SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.",
"author": "Dejnirattisai",
"doi-asserted-by": "crossref",
"first-page": "467",
"journal-title": "Cell",
"key": "R8-20230802",
"volume": "185",
"year": "2022"
},
{
"DOI": "10.1038/s41586-021-04385-3",
"article-title": "Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.",
"author": "Cao",
"doi-asserted-by": "crossref",
"first-page": "657",
"journal-title": "Nature",
"key": "R9-20230802",
"volume": "602",
"year": "2022"
},
{
"DOI": "10.1016/j.cell.2022.12.018",
"article-title": "Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants.",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "279",
"journal-title": "Cell",
"key": "R10-20230802",
"volume": "186",
"year": "2022"
},
{
"DOI": "10.1126/science.abl4784",
"article-title": "An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19.",
"author": "Owen",
"doi-asserted-by": "crossref",
"first-page": "1586",
"journal-title": "Science",
"key": "R11-20230802",
"volume": "374",
"year": "2021"
},
{
"DOI": "10.1038/s41422-022-00618-w",
"article-title": "SARS-CoV-2 Omicron variant is highly sensitive to molnupiravir, nirmatrelvir, and the combination.",
"author": "Li",
"doi-asserted-by": "crossref",
"first-page": "322",
"journal-title": "Cell Res",
"key": "R12-20230802",
"volume": "32",
"year": "2022"
},
{
"DOI": "10.1126/scitranslmed.abl7430",
"article-title": "A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus.",
"author": "Fischer",
"doi-asserted-by": "crossref",
"first-page": "eabl7430",
"journal-title": "Sci Transl Med",
"key": "R13-20230802",
"volume": "14",
"year": "2022"
},
{
"DOI": "10.1056/NEJMoa2116044",
"article-title": "Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients.",
"author": "Bernal",
"doi-asserted-by": "crossref",
"first-page": "509",
"journal-title": "N Engl J Med",
"key": "R14-20230802",
"volume": "386",
"year": "2021"
},
{
"DOI": "10.1016/j.antiviral.2022.105252",
"article-title": "Remdesivir, molnupiravir and nirmatrelvir remain active against SARS-CoV-2 omicron and other variants of concern.",
"author": "Vangeel",
"doi-asserted-by": "crossref",
"first-page": "105252",
"journal-title": "Antiviral Res",
"key": "R15-20230802",
"volume": "198",
"year": "2022"
},
{
"DOI": "10.1056/NEJMc2201933",
"article-title": "Efficacy of antiviral agents against the SARS-CoV-2 omicron subvariant BA.2.",
"author": "Takashita",
"doi-asserted-by": "crossref",
"first-page": "1475",
"journal-title": "N Engl J Med",
"key": "R16-20230802",
"volume": "386",
"year": "2022"
},
{
"DOI": "10.1128/Spectrum.01537-21",
"article-title": "Broad-spectrum in vitro antiviral Activity of ODBG-P-RVn: an orally-available, lipid-modified monophosphate prodrug of remdesivir parent nucleoside (GS-441524).",
"author": "Lo",
"doi-asserted-by": "crossref",
"first-page": "e01537",
"journal-title": "Microbiol Spectr",
"key": "R17-20230802",
"volume": "9",
"year": "2021"
},
{
"DOI": "10.1021/acs.jmedchem.2c00117",
"article-title": "Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL protease inhibitor clinical candidate for Treating COVID-19.",
"author": "Unoh",
"doi-asserted-by": "crossref",
"first-page": "6499",
"journal-title": "J Med Chem",
"key": "R18-20230802",
"volume": "65",
"year": "2022"
},
{
"article-title": "COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022.",
"author": "Wang",
"journal-title": "medRxiv",
"key": "R19-20230802",
"year": "2022"
},
{
"DOI": "10.1136/bmj.o926",
"article-title": "Covid-19: what is the evidence for the antiviral molnupiravir?",
"author": "Extance",
"doi-asserted-by": "crossref",
"first-page": "o926",
"journal-title": "BMJ",
"key": "R20-20230802",
"volume": "377",
"year": "2022"
},
{
"DOI": "10.1038/s41594-021-00651-0",
"article-title": "Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis.",
"author": "Kabinger",
"doi-asserted-by": "crossref",
"first-page": "740",
"journal-title": "Nat Struct Mol Biol",
"key": "R21-20230802",
"volume": "28",
"year": "2021"
},
{
"DOI": "10.1038/s41467-021-26760-4",
"article-title": "Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferrets.",
"author": "Cox",
"doi-asserted-by": "crossref",
"first-page": "6415",
"journal-title": "Nat Commun",
"key": "R22-20230802",
"volume": "12",
"year": "2021"
},
{
"DOI": "10.1002/bdr2.2111",
"article-title": "Developmental toxicity of remdesivir, an anti-COVID-19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells.",
"author": "Kirkwood-Johnson",
"doi-asserted-by": "crossref",
"first-page": "224",
"journal-title": "Birth Defects Res",
"key": "R23-20230802",
"volume": "115",
"year": "2022"
},
{
"DOI": "10.1016/j.phrs.2022.106201",
"article-title": "COVID-19 and the promise of small molecule therapeutics: are there lessons to be learnt?",
"author": "Ho",
"doi-asserted-by": "crossref",
"first-page": "106201",
"journal-title": "Pharmacol Res",
"key": "R24-20230802",
"volume": "179",
"year": "2022"
},
{
"DOI": "10.1016/S2213-2600(22)00192-8",
"article-title": "The future of Paxlovid for COVID-19.",
"author": "Burki",
"doi-asserted-by": "crossref",
"first-page": "e68",
"journal-title": "Lancet Respir Med",
"key": "R25-20230802",
"volume": "10",
"year": "2022"
},
{
"DOI": "10.1016/S1473-3099(22)00119-0",
"article-title": "Availability of oral antivirals against SARS-CoV-2 infection and the requirement for an ethical prescribing approach.",
"author": "Dal-Ré",
"doi-asserted-by": "crossref",
"first-page": "e231",
"journal-title": "Lancet Infect Dis",
"key": "R26-20230802",
"volume": "22",
"year": "2022"
},
{
"DOI": "10.1056/NEJMoa2208822",
"article-title": "VV116 versus nirmatrelvir-ritonavir for oral treatment of Covid-19.",
"author": "Cao",
"doi-asserted-by": "crossref",
"first-page": "406",
"journal-title": "N Engl J Med",
"key": "R27-20230802",
"volume": "388",
"year": "2022"
},
{
"DOI": "10.1038/s41591-022-01855-7",
"article-title": "Modeling transmission of SARS-CoV-2 omicron in China.",
"author": "Cai",
"doi-asserted-by": "crossref",
"first-page": "1468",
"journal-title": "Nat Med",
"key": "R28-20230802",
"volume": "28",
"year": "2022"
},
{
"DOI": "10.1021/acs.chemrev.1c00795",
"article-title": "Recent developments for the deuterium and tritium labeling of organic molecules.",
"author": "Kopf",
"doi-asserted-by": "crossref",
"first-page": "6634",
"journal-title": "Chem Rev",
"key": "R29-20230802",
"volume": "122",
"year": "2022"
},
{
"DOI": "10.1021/acs.jmedchem.0c00048",
"article-title": "Insights into PPARγ phosphorylation and its inhibition mechanism.",
"author": "Montanari",
"doi-asserted-by": "crossref",
"first-page": "4811",
"journal-title": "J Med Chem",
"key": "R30-20230802",
"volume": "63",
"year": "2020"
},
{
"DOI": "10.1038/s41422-021-00570-1",
"article-title": "Design and development of an oral remdesivir derivative VV116 against SARS-CoV-2.",
"author": "Xie",
"doi-asserted-by": "crossref",
"first-page": "1212",
"journal-title": "Cell Res",
"key": "R31-20230802",
"volume": "31",
"year": "2021"
},
{
"DOI": "10.1007/s40262-021-00984-5",
"article-title": "Pharmacokinetic, pharmacodynamic, and drug-interaction profile of remdesivir, a SARS-CoV-2 Replication Inhibitor.",
"author": "Humeniuk",
"doi-asserted-by": "crossref",
"first-page": "569",
"journal-title": "Clin Pharmacokinet",
"key": "R32-20230802",
"volume": "60",
"year": "2021"
},
{
"DOI": "10.1016/j.jpba.2023.115340",
"article-title": "Characterization of in-vivo human metabolites of the oral nucleoside anti-COVID-19 drug VV116 using UHPLC-Orbitrap-MS.",
"author": "Zhou",
"doi-asserted-by": "crossref",
"first-page": "115340",
"journal-title": "J Pharm Biomed Anal",
"key": "R33-20230802",
"volume": "228",
"year": "2023"
},
{
"DOI": "10.1038/s41401-022-00895-6",
"article-title": "Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects.",
"author": "Qian",
"doi-asserted-by": "crossref",
"first-page": "3130",
"journal-title": "Acta Pharmacol Sin",
"key": "R34-20230802",
"volume": "43",
"year": "2022"
},
{
"DOI": "10.1016/S0004-9514(14)60281-6",
"article-title": "Evidence for physiotherapy practice: a survey of the Physiotherapy Evidence Database (PEDro).",
"author": "Moseley",
"doi-asserted-by": "crossref",
"first-page": "43",
"journal-title": "Aust J Physiother",
"key": "R35-20230802",
"volume": "48",
"year": "2002"
},
{
"DOI": "10.3390/ijerph20032630",
"article-title": "Effects of equine-assisted activities and therapies for individuals with autism spectrum disorder: systematic review and meta-analysis.",
"author": "Xiao",
"doi-asserted-by": "crossref",
"first-page": "2630",
"journal-title": "Int J Environ Res Public Health",
"key": "R36-20230802",
"volume": "20",
"year": "2023"
},
{
"DOI": "10.1007/s40489-018-0130-z",
"article-title": "Effects of equine therapy on individuals with autism spectrum disorder: a systematic review.",
"author": "Srinivasan",
"doi-asserted-by": "crossref",
"first-page": "156",
"journal-title": "Rev J Autism Dev Disord",
"key": "R37-20230802",
"volume": "5",
"year": "2018"
},
{
"DOI": "10.1016/j.jaad.2012.02.010",
"article-title": "Grading dermatologic adverse events of cancer treatments: the common terminology criteria for adverse events Version 4.0.",
"author": "Chen",
"doi-asserted-by": "crossref",
"first-page": "1025",
"journal-title": "J Am Acad Dermatol",
"key": "R38-20230802",
"volume": "67",
"year": "2012"
},
{
"DOI": "10.1021/acsomega.2c04160",
"article-title": "Deuterated drugs and biomarkers in the COVID-19 Pandemic.",
"author": "Jansen-van Vuuren",
"doi-asserted-by": "crossref",
"first-page": "41840",
"journal-title": "ACS Omega",
"key": "R39-20230802",
"volume": "7",
"year": "2022"
}
],
"reference-count": 39,
"references-count": 39,
"relation": {},
"resource": {
"primary": {
"URL": "https://journals.lww.com/10.1097/MD.0000000000034105"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [
"General Medicine"
],
"subtitle": [],
"title": "The safety and efficacy of oral antiviral drug VV116 for treatment of COVID-19: A systematic review",
"type": "journal-article",
"volume": "102"
}
