Structural interactions between pandemic SARS-CoV-2 spike glycoprotein and human Furin protease

Vankadari, Naveen

doi:10.1101/2020.04.10.036533

Cited by 4 publications

(4 citation statements)

References 13 publications

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“… 57 Vankadari and Naveen in their 2020 preprint studies express furin as a Ca2+ dependent protease, which is highly expressed in lung cystic fibrosis disorder, and it is involved in the cleavage of SARS-CoV-2 viral glycoprotein. 58 The availability of furin-like cleavage at S1/S2 site of viruses, including SARS-CoV-2 contributes to the pathogenesis of the virus. 57 SARS-CoV-2 utilizes furin for the cleavage of S protein at the S1/S2 site.…”

Section: Proteins Involved In Viral Entry Mechanismmentioning

confidence: 99%

Role of Serine Proteases and Host Cell Receptors Involved in Proteolytic Activation, Entry of SARS-CoV-2 and Its Current Therapeutic Options

Dessie¹,

Malik²

2021

IDR

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The current global pandemic of a novel severe acute respiratory syndrome coronavirus-2 continues with its public health disaster beginning from late December 2019 in Wuhan, Hubei province, China. The scientific community has tried to fight against this novel coronavirus through vaccine development and designing different candidate drugs. However, there is no well-defined therapy to prevent 2019-nCov infection, thus complete prevention of the virus remains difficult. Therefore, it is a critical factor for death of millions worldwide. Many clinical trials and insights are ongoing in the struggle with this pandemic of SARS-CoV-2. SARS-CoV-2 entry into the host cell requires host cell angiotensinconverting enzyme-2 (ACE2) and glucose regulated protein 78 (GRP78). On the other hand, proteolytic activation of the viral spike protein (S protein) needs the host cell serine proteases, including transmembrane serine protease 2 (TMPRSS2), cathepsins, trypsin and furin. This review focuses on the protein involved in the mechanism of entry, and proteolytic activation. In addition, it looks at current therapeutic options for SARS-CoV-2.

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Section: Proteins Involved In Viral Entry Mechanismmentioning

confidence: 99%

Role of Serine Proteases and Host Cell Receptors Involved in Proteolytic Activation, Entry of SARS-CoV-2 and Its Current Therapeutic Options

Dessie¹,

Malik²

2021

IDR

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“…Coutard et al identified a furinlike cutting site in the SARS-CoV-2-S which is not available in other SARS-like CoVs such as Pangolin, Bat-CoV, and SARS-CoV-1. MERS has a pseudo-furin-binding site (Coutard et al, 2020;Vankadari, 2020). Likewise, Vankadari found that structurally, furin interacts with the SARS-CoV-2-S that highlighted the mechanism of viral host cell entry (Vankadari, 2020).…”

Section: The Functional Role Of Host Proteases In Sars-cov-2 Infectionmentioning

confidence: 97%

“…MERS has a pseudo-furin-binding site (Coutard et al, 2020;Vankadari, 2020). Likewise, Vankadari found that structurally, furin interacts with the SARS-CoV-2-S that highlighted the mechanism of viral host cell entry (Vankadari, 2020).…”

Section: The Functional Role Of Host Proteases In Sars-cov-2 Infectionmentioning

confidence: 97%

Host Serine Proteases: A Potential Targeted Therapy for COVID-19 and Influenza

Saadat

Khatibi

Vahed

et al. 2021

Front. Mol. Biosci.

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The ongoing pandemic illustrates limited therapeutic options for controlling SARS-CoV-2 infections, calling a need for additional therapeutic targets. The viral spike S glycoprotein binds to the human receptor angiotensin-converting enzyme 2 (ACE2) and then is activated by the host proteases. Based on the accessibility of the cellular proteases needed for SARS-S activation, SARS-CoV-2 entrance and activation can be mediated by endosomal (such as cathepsin L) and non-endosomal pathways. Evidence indicates that in the non-endosomal pathway, the viral S protein is cleaved by the furin enzyme in infected host cells. To help the virus enter efficiently, the S protein is further activated by the serine protease 2 (TMPRSS2), provided that the S has been cleaved by furin previously. In this review, important roles for host proteases within host cells will be outlined in SARS-CoV-2 infection and antiviral therapeutic strategies will be highlighted. Although there are at least five highly effective vaccines at this time, the appearance of the new viral mutations demands the development of therapeutic agents. Targeted inhibition of host proteases can be used as a therapeutic approach for viral infection.

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“…The spike proteins of SARS-CoV-2 has high affinity to the cellular receptor angiotensin-converting enzyme 2 (ACE2) for their entry inside the cells [4]. The higher binding affinity of SARS-CoV-2 spike protein to the human receptor ACE2 is due to presence of functional polybasic furin cleavage site at the S1-S2 boundary in the spike glycoprotein [5]. Zoonosis is common among CoVs and they can be transmitted from one animal species to another, animals to humans, and humans to humans [6; 7].…”

mentioning

confidence: 99%

Evaluation of Yashtimadhu (Glycyrrhiza glabra) active Phytochemicals Against Novel Coronavirus (SARS-CoV-2)

Maurya

2020

Preprint

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Corona Virus Disease 2019 (COVID-19) caused by a novel coronavirus emerged from Wuhan, China in December 2019. It has spread to more than 205 countries and become pandemic now. Currently, there are no FDA approved drugs or vaccines available and hence several studies are going on in search of suitable drug that can target viral proteins or host receptor for the prevention and management of COVID-19. The search for plant-based anti-viral agents against the SARS-CoV-2 is promising because several of plants have been shown to possess anti-viral activities against different viruses. Here, we used molecular docking approach to explore the use of Indian Ayurvedic herbs, Yashtimadhu in prevention and management of COVID-19. In the present study we have evaluated the effectiveness of phytochemicals found in Yashtimadhu against Main Protease (Mpro), Spike (S) protein and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 as well as human angiotensin converting enzyme 2 (ACE2) receptor and furin protease. Apart from this, we have also performed in-silico drug-likeness and predicted pharmacokinetics of the selected phytochemicals found in the Yashtimadhu. Our study shows that several phytochemicals found in this plant have potential to bind with important proteins of SARS-CoV-2 which are essential for viral infection and replication. Overall our study provides scientific basis in terms of binding of active ingredients present in Yashtimadhu with SARS-CoV-2 target proteins. Our docking studies reveal that Yashtimadhu may inhibit the viral severity by interfering with viral entry as well as its multiplication in the infected persons. Thus Yashtimadhu may be helpful in the prevention and management of the COVID-19.

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Structural interactions between pandemic SARS-CoV-2 spike glycoprotein and human Furin protease

Cited by 4 publications

References 13 publications

Role of Serine Proteases and Host Cell Receptors Involved in Proteolytic Activation, Entry of SARS-CoV-2 and Its Current Therapeutic Options

Role of Serine Proteases and Host Cell Receptors Involved in Proteolytic Activation, Entry of SARS-CoV-2 and Its Current Therapeutic Options

Host Serine Proteases: A Potential Targeted Therapy for COVID-19 and Influenza

Evaluation of Yashtimadhu (Glycyrrhiza glabra) active Phytochemicals Against Novel Coronavirus (SARS-CoV-2)

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