The ApoA-I mimetic peptide 4F attenuates in vitro replication of SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in epithelial cells (original) (raw)
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Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2
Nature Communications, 2021
Up to date, effective antivirals have not been widely available for treating COVID-19. In this study, we identify a dual-functional cross-linking peptide 8P9R which can inhibit the two entry pathways (endocytic pathway and TMPRSS2-mediated surface pathway) of SARS-CoV-2 in cells. The endosomal acidification inhibitors (8P9R and chloroquine) can synergistically enhance the activity of arbidol, a spike-ACE2 fusion inhibitor, against SARS-CoV-2 and SARS-CoV in cells. In vivo studies indicate that 8P9R or the combination of repurposed drugs (umifenovir also known as arbidol, chloroquine and camostat which is a TMPRSS2 inhibitor), simultaneously interfering with the two entry pathways of coronaviruses, can significantly suppress SARS-CoV-2 replication in hamsters and SARS-CoV in mice. Here, we use drug combination (arbidol, chloroquine, and camostat) and a dual-functional 8P9R to demonstrate that blocking the two entry pathways of coronavirus can be a promising and achievable approach fo...
SARS-CoV-2: Pathophysiology, Prophylaxis and Treatment Opportunities -A Current Review
International Journal of Advanced Science and Engineering, 2022
Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) was emerged in 2003, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) got reported in the year 2012. Following, SARS-CoV-2 was observed as pandemic around the globe in the end of 2019. COVID-19 has produced significant rate of morbidity and mortality rate causing severe loss of life. An immediate attention is required to find out active therapeutic methods and appropriate vaccines to control this epidemic condition. This is the crucial time to find out the lead compounds for the inhibition of SARS-CoV-2 by targeting its enzymes. The present review will make it possible to better understand the pathogenesis caused by the virus through their various proteins and finding path for the development of effective new drug targets and vaccines for this newly raised pathogen. In order to achieve these objectives, the current review will focus on the biology of the virus and describe the chemistry of a cellular targeted drug delivery pattern of two novel drug conjugates: HA-2-Deoxy-D-Glucose and HA-Hydroxychloroquine for treatment of COVID-19.
Potential of antiviral peptide-based SARS-CoV-2 inactivators to combat COVID-19
PLOS ONE
The appearance of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lack of effective antiviral therapeutics for coronavirus disease 2019 (COVID-19), a highly infectious disease caused by the virus, demands the search for alternative therapies. Most antiviral drugs known are passive defenders which must enter the cell to execute their function and suffer from concerns such as permeability and effectiveness, therefore in this current study, we aim to identify peptide inactivators that can act without entering the cells. SARS-CoV-2 spike protein is an essential protein that plays a major role in binding to the host receptor angiotensin-converting enzyme 2 and mediates the viral cell membrane fusion process. SARS vaccines and treatments have also been developed with the spike protein as a target. The virtual screening experiment revealed antiviral peptides which were found to be non-allergen, non-toxic and possess good water solubility. U-1, GST-remov...
Potential therapeutic and pharmacological strategies for SARS-CoV2
Journal of Pharmaceutical Investigation
Background At the end of 2019, the new Coronavirus disease 2019 (COVID-19) strain causing severe acute respiratory syndrome swept the world. From November 2019 till February 2021, this virus infected nearly 104 million, with more than two million deaths and about 25 million active cases. This has prompted scientists to discover effective drugs to combat this pandemic. Area covered Drug repurposing is the magic bullet for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Therefore, several drugs have been investigated in silico, in vitro, as well as through human trials such as anti-SARS-CoV2 agents, or to prevent the complications resulting from the virus. In this review, the mechanisms of action of different therapeutic strategies are summarized. According to the WHO, different classes of drugs can be used, including anti-malarial, antiviral, anti-inflammatory, and anti-coagulant drugs, as well as angiotensin-converting enzyme inhibitors, antibiotics, vitamins, zinc, neutralizing antibodies, and convalescent plasma therapy. Recently, there are some vaccines which are approved against SARS-CoV2. Expert opinion A complete understanding of the structure and function of all viral proteins that play a fundamental role in viral infection, which contribute to the therapeutic intervention and the development of vaccine in order to reduce the mortality rate.
The global coronavirus pandemic has posed serious challenges to entire world especially to the healthcare community. The widespread distribution of this virus has led to a major public health concern globally. In response to this crisis we have very rare specific tools to control the growing epidemic and treat those who are sick. We rely on quarantine, isolation, and infection-control measures to prevent disease spread and on supportive care for those who become ill. Now the race is to find viable strategies to discover potential candidate drugs to improve the immune system of patients to win the fight against SARS CoV-2, but at present no specific antiviral treatments or vaccines have been confirmed effective. In current situation while the whole mankind is eagerly waiting for a suitable vaccine, drugs presently being used to treat other diseases can be scrutinized as treatment option for COVID-19 pandemic. Although researchers all over the world are working to investigate the key features, pathogenesis and treatment options, it is deemed necessary to focus on existing competitive therapeutic options and cross-resistance of other viral drugs or vaccines. Here we summarized various promising candidates which are currently being used to treat other illnesses but can be a game changer in case of SARS CoV-2 virus to tackle this emergency. This review on recent updates will surely downsize the translational gap between preclinical testing results and clinical outcomes, which is a notable problem in the rapid development of an effective treatment options to fight this global crises.
Discovery of Small Anti‐ACE2 Peptides to Inhibit SARS‐CoV‐2 Infectivity
Advanced Therapeutics, 2021
COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infects host cells by binding its viral spike protein receptor-binding domain (RBD) to the angiotensin converting enzyme 2 (ACE2) on host cells. Blocking the SARS-CoV-2-RBD/ACE2 interaction is, therefore, a potential strategy to inhibit viral infections. Using a novel biopanning strategy, a small anti-ACE2 peptide is discovered, which shows high affinity and specificity to human ACE2. It blocks not only the SARS-CoV-2-RBD/ACE2 interaction but also the SARS-CoV-1-RBD/ACE2 interaction. Moreover, it inhibits SARS-CoV-2 infection in Vero-E6 cells. The peptide shows negligible cytotoxicity in Vero-E6 cells and Huh7 cells. In vivo short-term lung toxicity study also demonstrates a good safety of the peptide after intratracheal administration. The anti-ACE2 peptide can be potentially used as a prophylactic or therapeutic agent for SARS-CoV-2 or other ACE2-mediated viruses. The strategy used in this study also provides a fast-track platform to discover other antiviral peptides, which will prepare the world for future pandemics.
Peptide Antidotes to SARS-CoV-2 (COVID-19)
biorXiv, 2020
The design of an immunogenic scaffold that serves a role in treating a pathogen, and can be rapidly and predictively modeled, has remained an elusive feat. Here, we demonstrate that SARS-BLOCK™ synthetic peptide scaffolds act as antidotes to SARS-CoV-2 spike protein-mediated infection of human ACE2-expressing cells. Critically, SARS-BLOCK™ peptides are able to potently and competitively inhibit SARS-CoV-2 S1 spike protein receptor binding domain (RBD) binding to ACE2, the main cellular entry pathway for SARS-CoV-2, while also binding to neutralizing antibodies against SARS-CoV-2. In order to create this potential therapeutic antidote-vaccine, we designed, simulated, synthesized, modeled epitopes, predicted peptide folding, and characterized behavior of a novel set of synthetic peptides. The biomimetic technology is modeled off the receptor binding motif of the SARS-CoV-2 coronavirus, and modified to provide enhanced stability and folding versus the truncated wildtype sequence. These novel peptides attain single-micromolar binding affinities for ACE2 and a neutralizing antibody against the SARS-CoV-2 receptor binding domain (RBD), and demonstrate significant reduction of infection in nanomolar doses. We also demonstrate that soluble ACE2 abrogates binding of RBD to neutralizing antibodies, which we posit is an essential immune-evasive mechanism of the virus. SARS-BLOCK™ is designed to "uncloak" the viral ACE2 coating mechanism, while also binding to neutralizing antibodies with the intention of stimulating a specific neutralizing antibody response. Our peptide scaffolds demonstrate promise for future studies evaluating specificity and sensitivity of immune responses to our antidote-vaccine. In summary, SARS-BLOCK™ peptides are a promising COVID-19 antidote designed to combine the benefits of a therapeutic and vaccine, effectively creating a new generation of prophylactic and reactive antiviral therapeutics whereby immune responses can be enhanced rather than blunted.
Inflammatory pathways and potential therapies for COVID-19: A mini review
European Journal of Inflammation
The public health crisis of the novel coronavirus disease (COVID-19) is alarming since January 2020. COVID-19 genome (SARS-CoV-2) is related to other highly pathogenic coronaviruses SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus). Amino acid substitutions in some of SARS-CoV-2 proteins resulted in mutations proposing more virulent and contagious properties for this novel virus. Coronavirus penetrates the host cell via endocytosis and once infected, immune responses are triggered to fight against the pathogen. Innate immune response activates major transcription factors to secrete proinflammatory cytokines and type 1 interferon response (T1INF) to induce antiviral immunity. While adaptive immunity initiates cascade of B-cells antibody mediated and T-cells cellular mediate immunities, several mechanisms are raised by SARS-CoV-2 to evade host immune response. Consequently, a surge of proinflammatory cytokines, known a...
Life Sciences, 2020
The present pandemic of SARS-CoV-2 has been a tough task for the whole world to deal with. With the absence of specific drugs or vaccines against SARS-CoV-2, the situation is very difficult to control. Apart from the absence of specific therapies, the lack of knowledge about potential therapeutic targets and individual perception is adding to the complications. The present review describes the novel SARS-CoV-2 structure, surface proteins, asymptomatic and symptomatic transmission in addition to the genotype and phenotype of SARS-CoV-2 along with genetic strains and similarity between SARS, MERS and SARS-CoV-2. Therapeutic strategies such as inhibition of the endocytic pathway and suppressing RNA polymerase activity by metal ions, which could be quite beneficial for controlling COVID-19, are outlined. The drug repurposing for SARS-CoV-2 is discussed in detail along with therapeutic classes such as antivirals, antibiotics, and amino quinolones and their probable role in suppressing SARS-CoV-2 with reference to case studies. The ongoing clinical trials both with respect to drug repurposing and vaccines are summarized along with a brief description. The recent advancements and future perspective of ongoing research for therapy and detection of SARS-CoV-2 are provided. The review, in brief, summarizes epidemiology, therapy and the current scenario for combating SARS-CoV-2.