Repurposing old drugs as antiviral agents for coronaviruses

Yang, Cheng‐Wei; Peng, Tzu Ting; Hsu, Hsing Yu; Lee, Yue Zhi; Wu, Szu Huei; Lin, Wen Hsing; Ke, Yi Yu; Hsu, Tsu; Yeh, Teng Kuang; Huang, Wenzhun; Lin, Jau-Hong; Sytwu, Huey Kang; Chen, Chiung Tong; Lee, Shiow Ju

doi:10.1016/j.bj.2020.05.003

Cited by 65 publications

(52 citation statements)

References 37 publications

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“…The symptoms of SARS-CoV-2 such as reduced blood pressure following coma, induction of platelet aggregation and increased blood coagulability has been observed which was found to be associated with the ATP lowering effect of Nsp9 (Romano et al, 2020 ). Recently, conivaptan, an arginine vasopressin antagonist has been reported to exhibit high binding energy with Nsp9 and has shown antiviral activity against Human coronavirus OC43 (Chandel et al, 2020 ; Yang, Peng, et al, 2020 ). Hence, targeting Nsp9 seems to be a potential strategy for therapeutic armamentarium of the COVID-19 infection (Littler et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Anin-silicoanalysis of ivermectin interaction with potential SARS-CoV-2 targets and host nuclear importin α

Azam

Taban

Eid

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Ivermectin (IVM) is a broad-spectrum antiparasitic agent, having inhibitory potential against wide range of viral infections. It has also been found to hamper SARS-CoV-2 replication in vitro, and its precise mechanism of action against SARS-CoV-2 is yet to be understood. IVM is known to interact with host importin (IMP)α directly and averts interaction with IMPβ1, leading to the prevention of nuclear localization signal (NLS) recognition. Therefore, the current study seeks to employ molecular docking, molecular mechanics generalized Born surface area (MM-GBSA) analysis and molecular dynamics simulation studies for decrypting the binding mode, key interacting residues as well as mechanistic insights on IVM interaction with 15 potential drug targets associated with COVID-19 as well as IMPα. Among all COVID-19 targets, the non-structural protein 9 (Nsp9) exhibited the strongest affinity to IVM showing −5.30 kcal/mol and −84.85 kcal/mol binding energies estimated by AutoDock Vina and MM-GBSA, respectively. However, moderate affinity was accounted for IMPα amounting −6.9 kcal/mol and −66.04 kcal/mol. Stability of the protein-ligand complexes of Nsp9-IVM and IMPα-IVM was ascertained by 100 ns trajectory of all-atom molecular dynamics simulation. Structural conformation of protein in complex with docked IVM exhibited stable root mean square deviation while root mean square fluctuations were also found to be consistent. In silico exploration of the potential targets and their interaction profile with IVM can assist experimental studies as well as designing of COVID-19 drugs. Communicated by Ramaswamy H. Sarma

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Section: Resultsmentioning

confidence: 99%

Anin-silicoanalysis of ivermectin interaction with potential SARS-CoV-2 targets and host nuclear importin α

Azam

Taban

Eid

et al. 2020

Journal of Biomolecular Structure and Dynamics

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“…These cases may represent a repositioning of the drugs with clinical success in treatment areas beyond their original approved use. According to this, the antiviral in vitro activity of spermidine, niclosamide, and nitazoxanide (known autophagy inducers) vs. SARS-CoV-2 was recently reported (Shakya et al, 2018;Liu et al, 2019;Xu et al, 2020;Yang et al, 2020). Thus, a prophylactic approach to COVID-19 using these drugs, which are well tolerated, clinically applied, or FDA-approved compounds, would be rational (Gassen et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, different drugs described as inhibitors or inducers of the autophagy that control host cell pathways process involved in coronavirus infection, have sparked interest for their potential antiviral activity ( Shakya et al, 2018 ; Liu et al, 2019 ; Xu et al, 2020 ; Yang et al, 2020 ; Table 1 ). One of this, chloroquine (CQ), and its derivative hydroxychloroquine (HCQ), known as anti-malarial drugs ( O’Neill et al, 1998 ), which are able to inhibit autophagy by raising the lysosomal pH ( Golden et al, 2015 ), have also been evaluated for HIV infection ( Romanelli et al, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Coronavirus Interplay With Lipid Rafts and Autophagy Unveils Promising Therapeutic Targets

et al. 2020

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Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses that can infect animal and human hosts. The infection induces mild or sometimes severe acute respiratory diseases. Nowadays, the appearance of a new, highly pathogenic and lethal coronavirus variant, SARS-CoV-2, responsible for a pandemic (COVID-19), represents a global problem for human health. Unfortunately, only limited approaches are available to treat coronavirus infections and a vaccine against this new coronavirus variant is not yet available. The plasma membrane microdomain lipid rafts have been found by researchers to be involved in the replication cycle of numerous viruses, including coronaviruses. Indeed, some pathogen recognition receptors for coronaviruses as for other viruses cluster into lipid rafts, and it is therefore conceivable that the first contact between virus and host cells occurs into these specialized regions, representing a port of cell entry for viruses. Recent data highlighted the peculiar pro-viral or anti-viral role played by autophagy in the host immune responses to viral infections. Coronaviruses, like other viruses, were reported to be able to exploit the autophagic machinery to increase their replication or to inhibit the degradation of viral products. Agents known to disrupt lipid rafts, such as metil-β-cyclodextrins or statins, as well as autophagy inhibitor agents, were shown to have an anti-viral role. In this review, we briefly describe the involvement of lipid rafts and autophagy in coronavirus infection and replication. We also hint how lipid rafts and autophagy may represent a potential therapeutic target to be investigated for the treatment of coronavirus infections.

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“…As treatment of COVID-19 is urgently required, one possible strategy is to repurpose existing anti-viral agents against the current COVID-19 infection [ 47 , 48 ]. Sayad et al suggested the use of sofosbuvir, an approved anti-hepatitis virus C agent, as a repurposed antiviral drug against SARS-CoV-2 infection [ 49 ].…”

Section: Pharmacologic Treatmentsmentioning

confidence: 99%

COVID-19: Current Developments and Further Opportunities in Drug Delivery and Therapeutics

et al. 2020

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SARS-CoV-2 has affected people from all age groups, races and ethnicities. Given that many infected individuals are asymptomatic, they transmit the disease to others unknowingly, which has resulted in the spread of infection at an alarming rate. This review aims to provide an overview of the pathophysiology, preventive measures to reduce the disease spread, therapies currently in use, an update on vaccine development and opportunities for vaccine delivery. The World Health Organization has advised several precautions including social distancing, hand washing and the use of PPE including gloves and face masks for minimizing the spread of SARS-CoV-2 infection. At present, several antiviral therapies previously approved for other infections are being repositioned to study their efficacy against SARS-CoV-2. In addition, some medicines (i.e., remdesivir, chloroquine, hydroxychloroquine) have received emergency use authorisation from the FDA. Plasma therapy has also been authorised for emergency use for the treatment of COVID-19 on a smaller scale. However, no vaccine has been approved so far against this virus. Nevertheless, several potential vaccine targets have been reported, and development of different types of vaccines including DNA, mRNA, viral vector, inactivated, subunit and vaccine-like particles is in process. It is concluded that a suitable candidate delivered through an advanced drug delivery approach would effectively boost the immune system against this coronavirus.

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Repurposing old drugs as antiviral agents for coronaviruses

Cited by 65 publications

References 37 publications

Anin-silicoanalysis of ivermectin interaction with potential SARS-CoV-2 targets and host nuclear importin α

Anin-silicoanalysis of ivermectin interaction with potential SARS-CoV-2 targets and host nuclear importin α

Coronavirus Interplay With Lipid Rafts and Autophagy Unveils Promising Therapeutic Targets

COVID-19: Current Developments and Further Opportunities in Drug Delivery and Therapeutics

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