Anno 2021: Which antivirals for the coming decade?

Groaz, Elisabetta; Clercq, Erik De; Herdewijn, Piet

doi:10.1016/bs.armc.2021.09.004

Cited by 11 publications

(10 citation statements)

References 253 publications

(262 reference statements)

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“…In this review, we focus on the development of antiviral strategies targeting the L protein, which orchestrate the replication and transcription, and we will only describe the most relevant and recent molecules. Exhaustive references of antivirals and a snapshot of the clinical interventions targeting RSV have been reviewed in (accessed date 9 January 2023) and [ 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 ] ( Figure 8 ). The current approaches to inhibiting the RSV polymerase include nucleoside and non-nucleoside analogs inhibitors that have been identified by screening compounds using infectious RSV, cell-based replicon assays, and in vitro assays that use the recombinant L–P complex and naked RNA as templates.…”

Section: Rsv L Antiviralsmentioning

confidence: 99%

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Biochemistry of the Respiratory Syncytial Virus L Protein Embedding RNA Polymerase and Capping Activities

Sutto-Ortiz

Éléouët

Ferrón

et al. 2023

Viruses

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The human respiratory syncytial virus (RSV) is a negative-sense, single-stranded RNA virus. It is the major cause of severe acute lower respiratory tract infection in infants, the elderly population, and immunocompromised individuals. There is still no approved vaccine or antiviral treatment against RSV disease, but new monoclonal prophylactic antibodies are yet to be commercialized, and clinical trials are in progress. Hence, urgent efforts are needed to develop efficient therapeutic treatments. RSV RNA synthesis comprises viral transcription and replication that are catalyzed by the large protein (L) in coordination with the phosphoprotein polymerase cofactor (P), the nucleoprotein (N), and the M2-1 transcription factor. The replication/transcription is orchestrated by the L protein, which contains three conserved enzymatic domains: the RNA-dependent RNA polymerase (RdRp), the polyribonucleotidyl transferase (PRNTase or capping), and the methyltransferase (MTase) domain. These activities are essential for the RSV replicative cycle and are thus considered as attractive targets for the development of therapeutic agents. In this review, we summarize recent findings about RSV L domains structure that highlight how the enzymatic activities of RSV L domains are interconnected, discuss the most relevant and recent antivirals developments that target the replication/transcription complex, and conclude with a perspective on identified knowledge gaps that enable new research directions.

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Section: Rsv L Antiviralsmentioning

confidence: 99%

“… Snapshot of the development of RSV clinical interventions. Adapted from the PATH website at (accessed date 9 January 2023) and [ 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 ]. …”

Section: Figurementioning

confidence: 99%

Biochemistry of the Respiratory Syncytial Virus L Protein Embedding RNA Polymerase and Capping Activities

Sutto-Ortiz

Éléouët

Ferrón

et al. 2023

Viruses

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“…Directly acting antivirals (DAA) that include small molecules and some antibodies, target virally encoded proteins directly and efficiently suppress viral replication in vivo [ 36 ] (reviewed in [ 37 , 38 ]). DAA commonly targets viral entry and fusion, or key enzymes like viral polymerases and proteases such as the SARS-CoV2 3-chymotrypsin-like protease (3CL pro ), also known as main protease (M pro ), and papain-like protease (PL pro ) [ 36 , 38 ]. By targeting viral replication directly, DAA are generally thought to have fewer side effects than HTA [ 39 ].…”

Section: Directly Acting Antivirals (Daa)mentioning

confidence: 99%

An Update on SARS-CoV-2 Clinical Trial Results—What We Can Learn for the Next Pandemic

Arman,

Brun,

Hill

et al. 2023

IJMS

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The coronavirus disease 2019 (COVID-19) pandemic has claimed over 7 million lives worldwide, providing a stark reminder of the importance of pandemic preparedness. Due to the lack of approved antiviral drugs effective against coronaviruses at the start of the pandemic, the world largely relied on repurposed efforts. Here, we summarise results from randomised controlled trials to date, as well as selected in vitro data of directly acting antivirals, host-targeting antivirals, and immunomodulatory drugs. Overall, repurposing efforts evaluating directly acting antivirals targeting other viral families were largely unsuccessful, whereas several immunomodulatory drugs led to clinical improvement in hospitalised patients with severe disease. In addition, accelerated drug discovery efforts during the pandemic progressed to multiple novel directly acting antivirals with clinical efficacy, including small molecule inhibitors and monoclonal antibodies. We argue that large-scale investment is required to prepare for future pandemics; both to develop an arsenal of broad-spectrum antivirals beyond coronaviruses and build worldwide clinical trial networks that can be rapidly utilised.

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“…Currently, various antiviral therapies have been developed to target different steps of the viral life cycle, including virus adsorption, fusion, and genomic replication so as to inhibit viral proliferation. [ 128 ] On this basis, it is necessary to further reduce inflammation, repair lung injury, and improve respiratory function, thereby achieving the purpose of relieving the disease and improving the survival rate of patients. In addition, clinical studies have shown that patients with COVID‐19, especially severe cases, generally suffer from lymphopenia, which in turn leads to the inability to completely clear the virus in the body, resulting in aggravation of the disease.…”

Section: Applications Of Cell‐based Biomaterials In Coronavirus Disea...mentioning

confidence: 99%

Cell‐Based Biomaterials for Coronavirus Disease 2019 Prevention and Therapy

Wang

Xie

et al. 2023

Adv Healthcare Materials

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Coronavirus disease 2019 (COVID-19) continues to threaten human health, economic development, and national security. Although many vaccines and drugs have been explored to fight against the major pandemic, their efficacy and safety still need to be improved. Cell-based biomaterials, especially living cells, extracellular vesicles, and cell membranes, offer great potential in preventing and treating COVID-19 owing to their versatility and unique biological functions. In this review, the characteristics and functions of cell-based biomaterials and their biological applications in COVID-19 prevention and therapy are described. First the pathological features of COVID-19 are summarized, providing enlightenment on how to fight against COVID-19. Next, the classification, organization structure, characteristics, and functions of cell-based biomaterials are focused on. Finally, the progress of cell-based biomaterials in overcoming COVID-19 in different aspects, including the prevention of viral infection, inhibition of viral proliferation, anti-inflammation, tissue repair, and alleviation of lymphopenia are comprehensively described. At the end of this review, a look forward to the challenges of this aspect is presented.

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Anno 2021: Which antivirals for the coming decade?

Cited by 11 publications

References 253 publications

Biochemistry of the Respiratory Syncytial Virus L Protein Embedding RNA Polymerase and Capping Activities

Biochemistry of the Respiratory Syncytial Virus L Protein Embedding RNA Polymerase and Capping Activities

An Update on SARS-CoV-2 Clinical Trial Results—What We Can Learn for the Next Pandemic

Cell‐Based Biomaterials for Coronavirus Disease 2019 Prevention and Therapy

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