Insights into SARS-CoV-2: Medicinal Chemistry Approaches to Combat Its Structural and Functional Biology

Zhuo, Lin-Sheng; Wang, Mingshu; Yang, Jing‐Fang; Xu, Haifeng; Huang, Wei; Shang, Luqing; Yang, Guang‐Fu

doi:10.1007/s41061-021-00335-9

Cited by 7 publications

(5 citation statements)

References 135 publications

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“…The cellular transmembrane protease serine 2 (TMPRSS2) is recruited to cleave the viral S protein enabling membrane fusion [ 8 ]. Novel therapeutic approaches are urgently needed: the blocking of the S protein interaction with the ACE2 receptor and the deactivation of processing via TMPRSS2 have been identified as potential strategies to prevent viral cell entry [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Activity of a Carbohydrate-Binding Module Therapy, Neumifil, against SARS-CoV-2 Disease in a Hamster Model of Infection

Fell¹,

Potter²,

Yuille³

et al. 2022

Viruses

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The rapid global spread of severe acute respiratory coronavirus 2 (SARS-CoV-2) has resulted in an urgent effort to find efficacious therapeutics. Broad-spectrum therapies which could be used for other respiratory pathogens confer advantages, as do those based on targeting host cells that are not prone to the development of resistance by the pathogen. We tested an intranasally delivered carbohydrate-binding module (CBM) therapy, termed Neumifil, which is based on a CBM that has previously been shown to offer protection against the influenza virus through the binding of sialic acid receptors. Using the recognised hamster model of SARS-CoV-2 infection, we demonstrate that Neumifil significantly reduces clinical disease severity and pathological changes in the nasal cavity. Furthermore, we demonstrate Neumifil binding to the human angiotensin-converting enzyme 2 (ACE2) receptor and spike protein of SARS-CoV-2. This is the first report describing the testing of this type of broad-spectrum antiviral therapy in vivo and provides evidence for the advancement of Neumifil in further preclinical and clinical studies.

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Section: Introductionmentioning

confidence: 99%

Activity of a Carbohydrate-Binding Module Therapy, Neumifil, against SARS-CoV-2 Disease in a Hamster Model of Infection

Fell¹,

Potter²,

Yuille³

et al. 2022

Viruses

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“…Arbidol ( Figure 2 ( 10 )) is an antiviral drug developed by the Soviet Medicinal Chemistry Research Center that can prevent the viral envelope from contacting, adhering to, and fusing with the host cell membrane [ 111 , 112 ]. The results of molecular dynamics simulation analysis show that arbidol with a high-affinity combination is able to stabilize at the interface between the receptor-binding domain (RBD) and ACE2.…”

Section: Drugs That Target Spike Glycoproteinsmentioning

confidence: 99%

Progress on COVID-19 Chemotherapeutics Discovery and Novel Technology

et al. 2022

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COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel highly contagious and pathogenic coronavirus that emerged in late 2019. SARS-CoV-2 spreads primarily through virus-containing droplets and small particles of air pollution, which greatly increases the risk of inhaling these virus particles when people are in close proximity. COVID-19 is spreading across the world, and the COVID-19 pandemic poses a threat to human health and public safety. To date, there are no specific vaccines or effective drugs against SARS-CoV-2. In this review, we focus on the enzyme targets of the virus and host that may be critical for the discovery of chemical compounds and natural products as antiviral drugs, and describe the development of potential antiviral drugs in the preclinical and clinical stages. At the same time, we summarize novel emerging technologies applied to the research on new drug development and the pathological mechanisms of COVID-19.

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“…As to these five viral targets, there is great hope to develop effective treatment strategies that would (1) interfere with the binding of viral Spike protein to the ACE2 receptor on the surface of host cells to prevent viral infection of cells [22,28], (2) inhibit the activity of PLpro and 3CLpro, interfering with their cleavage of multiple proteins to produce nonstructural proteins (NSPs) such as RdRp and helicase [29], (3) antagonize RdRp activity and block viral RNA transcription, synthesis and replication [25,30], and (4) interfere with the role of viral helicase and inhibit the replication of viral RNA [27]. Relying on these five viral protein targets to establish efficient drug screening methods may be convenient for finding natural products with anti-SARS-CoV-2 potential [31,32].…”

Section: Introductionmentioning

confidence: 99%

Development of Fluorescence-Based Assays for Key Viral Proteins in the SARS-CoV-2 Infection Process and Lifecycle

Deng,

Zhang,

Yan

et al. 2024

IJMS

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Since the appearance of SARS-CoV-2 in 2019, the ensuing COVID-19 (Corona Virus Disease 2019) pandemic has posed a significant threat to the global public health system, human health, life, and economic well-being. Researchers worldwide have devoted considerable efforts to curb its spread and development. The latest studies have identified five viral proteins, spike protein (Spike), viral main protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), and viral helicase (Helicase), which play crucial roles in the invasion of SARS-CoV-2 into the human body and its lifecycle. The development of novel anti-SARS-CoV-2 drugs targeting these five viral proteins holds immense promise. Therefore, the development of efficient, high-throughput screening methodologies specifically designed for these viral proteins is of utmost importance. Currently, a plethora of screening techniques exists, with fluorescence-based assays emerging as predominant contenders. In this review, we elucidate the foundational principles and methodologies underpinning fluorescence-based screening approaches directed at these pivotal viral targets, hoping to guide researchers in the judicious selection and refinement of screening strategies, thereby facilitating the discovery and development of lead compounds for anti-SARS-CoV-2 pharmaceuticals.

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Insights into SARS-CoV-2: Medicinal Chemistry Approaches to Combat Its Structural and Functional Biology

Cited by 7 publications

References 135 publications

Activity of a Carbohydrate-Binding Module Therapy, Neumifil, against SARS-CoV-2 Disease in a Hamster Model of Infection

Activity of a Carbohydrate-Binding Module Therapy, Neumifil, against SARS-CoV-2 Disease in a Hamster Model of Infection

Progress on COVID-19 Chemotherapeutics Discovery and Novel Technology

Development of Fluorescence-Based Assays for Key Viral Proteins in the SARS-CoV-2 Infection Process and Lifecycle

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