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Open accessJournal ArticleDOI: 10.1016/J.PEPTIDES.2021.170526

Antiviral peptides against Coronaviridae family: A review.

04 Mar 2021-Peptides (Elsevier)-Vol. 139, pp 170526-170526
Abstract: The Coronaviridae family comprises large enveloped single-stranded RNA viruses. The known human-infecting coronaviruses; severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), novel SARS-CoV-2, human coronavirus (HCoV)-NL63, HCoV-229E, HCoV-OC43 and HKU1 cause mild to severe respiratory infections. The viral diseases induced by mammalian and avian viruses from Coronaviridae family pose significant economic and public health burdens. Due to increasing reports of viral resistance, co-infections and the emergence of viral epidemics such as COVID-19, available antiviral drugs show low or no efficacy, and the production of new treatments or vaccines are also challenging. Therefore, demand for the development of novel antivirals has considerably increased. In recent years, antiviral peptides have generated increasing interest as they are from natural and computational sources, are highly specific and effective, and possess the broad-spectrum activity with minimum side effects. Here, we have made an effort to compile and review the antiviral peptides with activity against Coronaviridae family viruses. They were divided into different categories according to their action mechanisms, including binding/attachment inhibitors, fusion and entry inhibitors, viral enzyme inhibitors, replication inhibitors and the peptides with direct and indirect effects on the viruses. Reported studies suggest optimism with regard to the design and production of therapeutically promising antiviral drugs. This review aims to summarize data relating to antiviral peptides particularly with respect to their applicability for development as novel treatments.

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6 results found

Open accessJournal ArticleDOI: 10.1186/S13054-021-03662-X
Jasmin Khateeb1, Jasmin Khateeb2, Yuchong Li2, Yuchong Li3  +3 moreInstitutions (4)
12 Jul 2021-Critical Care
Abstract: The major variant of concerns (VOCs) have shared mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins, mostly on the S1 unit and resulted in higher transmissibility rate and affect viral virulence and clinical outcome. The spike protein mutations and other non-structural protein mutations in the VOCs may lead to escape approved vaccinations in certain extend. We will discuss these VOC mutations and discuss the need for combination therapeutic strategies targeting viral cycle and immune host responses.

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26 Citations

Open accessJournal ArticleDOI: 10.1016/J.PEPTIDES.2021.170638
Songling Han1, Gaomei Zhao1, Zhuanzhuan Wei1, Yin Chen1  +11 moreInstitutions (1)
19 Aug 2021-Peptides
Abstract: The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global concern and necessitates efficient drug antagonists. Angiotensin-converting enzyme-2 (ACE2) is the main receptor of SARS-CoV-2 spike 1 (S1), which mediates viral invasion into host cells. Herein, we designed and prepared short peptide inhibitors containing 4-6 critical residues of ACE2 that contribute to the interaction with SARS-CoV-2 S1. Among the candidates, a peptide termed GK-7 (GKGDFRI), which was designed by extracting residues ranging from Gly353 to Ile359 in the ligand-binding domain of ACE2, exhibited the highest binding affinity (25.1 nM) with the SARS-CoV-2 spike receptor-binding domain (RBD). GK-7 bound to the RBD and decreased SARS-CoV-2 S1 attachment to A549 human alveolar epithelial cells. Owing to spike blockade, GK-7 inhibited SARS-CoV-2 spike pseudovirion infection in a dose-dependent manner, with a half-maximal inhibitory concentration of 2.96 μg/mL. Inspiringly, pulmonary delivery of GK-7 by intranasal administration did not result in toxicity in mice. This study revealed an easy-to-produce peptide inhibitor for SARS-CoV-2 spike blockade, thus providing a promising candidate for COVID-19 treatment.

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1 Citations

Open accessJournal ArticleDOI: 10.3389/FMOLB.2021.732256
Topu Raihan1, Muhammad Fazle Rabbee2, Puja Roy1, Swapnila Choudhury3  +2 moreInstitutions (3)
Abstract: The present global COVID-19 pandemic caused by the noble pleomorphic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a vulnerable situation in the global healthcare and economy. In this pandemic situation, researchers all around the world are trying their level best to find suitable therapeutics from various sources to combat against the SARS-CoV-2. To date, numerous bioactive compounds from different sources have been tested to control many viral diseases. However, microbial metabolites are advantageous for drug development over metabolites from other sources. We herein retrieved and reviewed literatures from PubMed, Scopus and Google relevant to antiviral microbial metabolites by searching with the keywords "antiviral microbial metabolites," "microbial metabolite against virus," "microorganism with antiviral activity," "antiviral medicine from microbial metabolite," "antiviral bacterial metabolites," "antiviral fungal metabolites," "antiviral metabolites from microscopic algae' and so on. For the same purpose, the keywords "microbial metabolites against COVID-19 and SARS-CoV-2" and "plant metabolites against COVID-19 and SARS-CoV-2" were used. Only the full text literatures available in English and pertinent to the topic have been included and those which are not available as full text in English and pertinent to antiviral or anti-SARS-CoV-2 activity were excluded. In this review, we have accumulated microbial metabolites that can be used as antiviral agents against a broad range of viruses including SARS-CoV-2. Based on this concept, we have included 330 antiviral microbial metabolites so far available to date in the data bases and were previously isolated from fungi, bacteria and microalgae. The microbial source, chemical nature, targeted viruses, mechanism of actions and IC50/EC50 values of these metabolites are discussed although mechanisms of actions of many of them are not yet elucidated. Among these antiviral microbial metabolites, some compounds might be very potential against many other viruses including coronaviruses. However, these potential microbial metabolites need further research to be developed as effective antiviral drugs. This paper may provide the scientific community with the possible secret of microbial metabolites that could be an effective source of novel antiviral drugs to fight against many viruses including SARS-CoV-2 as well as the future viral pandemics.

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Open accessJournal ArticleDOI: 10.1016/J.LWT.2021.112684
Wenzhu Zhao1, Xin Li1, Zhipeng Yu1, Sijia Wu2  +2 moreInstitutions (3)
Abstract: COVID-19 is a global health emergency that causes serious concerns. A global effort is underway to identify drugs for the treatment of COVID-19. One possible solution to the present problem is to develop drugs that can inhibit SARS-CoV-2 main protease (Mpro), a coronavirus protein that been considered as one among many drug targets. In this work, lactoferrin from Bos taurus L. was in silico hydrolyzed. The bioactivity, water solubility, and ADMET properties of the generated peptides were predicted using various online tools. The molecular interactions between Mpro and the peptides were studied using molecular docking and molecular dynamic simulation. The results demonstrated that peptide GSRY was predicted to have better physicochemical properties, and the value of '-C DOCKER interaction energy' between peptide GSRY and Mpro was 80.8505 kcal/mol. The interaction between the peptide GSRY and the native ligand N3 co-crystallized with Mpro had overlapped amino acids, i.e., HIS163, GlY143, GLU166, GLN189 and MET165. Molecular dynamic simulation revealed that Mpro/GSRY complexes were stable. Collectively, the peptide GSRY may be a potential candidate drug against Mpro of SARS-CoV-2.

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Open accessJournal ArticleDOI: 10.3390/PH14080774
Nour Mammari1, Ysaline Krier, Quentin Albert2, Marc Devocelle  +1 moreInstitutions (2)
Abstract: Numerous studies have led to a better understanding of the mechanisms of action of viruses in systemic infections for the development of prevention strategies and very promising antiviral therapies. Viruses still remain one of the main causes of human diseases, mainly because the development of new vaccines is usually challenging and drug resistance has become an increasing concern in recent decades. Therefore, the development of potential antiviral agents remains crucial and is an unmet clinical need. One abundant source of potential therapeutic molecules are plants: they biosynthesize a myriad of compounds, including peptides which can have antimicrobial activity. Our objective is to summarize the literature on peptides with antiviral properties derived from plants and to identify key features of these peptides and their application in systemic viral infections. This literature review highlights studies including clinical trials which demonstrated that plant cyclotides have the ability to inhibit the growth of viruses causing human diseases, defensin-like peptides possess anti-HIV-1 activity, and lipid transfer proteins and some lectins exhibit a varied antimicrobial profile. To conclude, plant peptides remain interesting to explore in the context of emerging and re-emerging infectious diseases.

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Topics: Antimicrobial peptides (59%)


88 results found

Open accessJournal ArticleDOI: 10.1126/SCIENCE.ABB2507
13 Mar 2020-Science
Abstract: The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

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5,197 Citations

Open accessJournal ArticleDOI: 10.1038/S41579-018-0118-9
Jie Cui1, Fang Li2, Zhengli Shi1Institutions (2)
Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs. Coronaviruses have a broad host range and distribution, and some highly pathogenic lineages have spilled over to humans and animals. Here, Cui, Li and Shi explore the viral factors that enabled the emergence of diseases such as severe acute respiratory syndrome and Middle East respiratory syndrome.

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2,810 Citations

Open accessJournal ArticleDOI: 10.1128/JVI.77.16.8801-8811.2003
Abstract: Coronavirus entry is mediated by the viral spike (S) glycoprotein. The 180-kDa oligomeric S protein of the murine coronavirus mouse hepatitis virus strain A59 is posttranslationally cleaved into an S1 receptor binding unit and an S2 membrane fusion unit. The latter is thought to contain an internal fusion peptide and has two 4,3 hydrophobic (heptad) repeat regions designated HR1 and HR2. HR2 is located close to the membrane anchor, and HR1 is some 170 amino acids (aa) upstream of it. Heptad repeat (HR) regions are found in fusion proteins of many different viruses and form an important characteristic of class I viral fusion proteins. We investigated the role of these regions in coronavirus membrane fusion. Peptides HR1 (96 aa) and HR2 (39 aa), corresponding to the HR1 and HR2 regions, were produced in Escherichia coli. When mixed together, the two peptides were found to assemble into an extremely stable oligomeric complex. Both on their own and within the complex, the peptides were highly alpha helical. Electron microscopic analysis of the complex revealed a rod-like structure approximately 14.5 nm in length. Limited proteolysis in combination with mass spectrometry indicated that HR1 and HR2 occur in the complex in an antiparallel fashion. In the native protein, such a conformation would bring the proposed fusion peptide, located in the N-terminal domain of HR1, and the transmembrane anchor into close proximity. Using biological assays, the HR2 peptide was shown to be a potent inhibitor of virus entry into the cell, as well as of cell-cell fusion. Both biochemical and functional data show that the coronavirus spike protein is a class I viral fusion protein.

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Topics: Fusion protein (61%), Heptad repeat (57.99%), Coronavirus (57.99%) ... show more

1,049 Citations

Open accessJournal ArticleDOI: 10.3389/FCIMB.2016.00194
Abstract: Antimicrobial peptides (AMPs), also known as host defense peptides, are short and generally positively charged peptides found in a wide variety of life forms from microorganisms to humans. Most AMPs have the ability to kill microbial pathogens directly, whereas others act indirectly by modulating the host defense systems. Against a background of rapidly increasing resistance development to conventional antibiotics all over the world, efforts to bring AMPs into clinical use are accelerating. Several AMPs are currently being evaluated in clinical trials as novel anti-infectives, but also as new pharmacological agents to modulate the immune response, promote wound healing, and prevent post-surgical adhesions. In this review, we provide an overview of the biological role, classification, and mode of action of AMPs, discuss the opportunities and challenges to develop these peptides for clinical applications, and review the innovative formulation strategies for application of AMPs.

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Topics: Antimicrobial peptides (56%)

818 Citations

Open accessJournal ArticleDOI: 10.1038/S41422-020-0305-X
Shuai Xia1, Meiqin Liu2, Chao Wang, Wei Xu1  +13 moreInstitutions (5)
30 Mar 2020-Cell Research
Abstract: The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell–cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.

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Topics: Plasma membrane fusion (61%), Coronavirus (57.99%), Cell fusion (53%) ... show more

708 Citations