Coronavirus membrane fusion mechanism offers a potential target for antiviral development

Antiviral Research, Journal Year: 2020, Volume and Issue: 178, P. 104792 - 104792

Published: April 6, 2020

Language: Английский

---

Inhibitors of SARS-CoV-2 Entry: Current and Future Opportunities

Journal of Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 63(21), P. 12256 - 12274

Published: June 15, 2020

Recently, a novel coronavirus initially designated 2019-nCoV but now termed SARS-CoV-2 has emerged and raised global concerns due to its virulence. is the etiological agent of "coronavirus disease 2019", abbreviated COVID-19, which despite only being identified at very end 2019, been classified as pandemic by World Health Organization (WHO). At this time, no specific prophylactic or postexposure therapy for COVID-19 are currently available. Viral entry first step in lifecycle mediated trimeric spike protein. Being stage infection, into host cells an extremely attractive therapeutic intervention point. Within review, we highlight strategies anti-SARS-CoV, MERS-CoV, other coronaviruses speculate upon future directions inhibitor designs.

Language: Английский

---

Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo

Journal of Virology, Journal Year: 2020, Volume and Issue: 94(21)

Published: Aug. 20, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China at the end of 2019 and has rapidly caused a pandemic, with over 20 million recorded COVID-19 cases August 2020 (https://covid19.who.int/). There are no FDA-approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments limited to supportive therapies off-label use drugs. Rapid development human testing potential is urgently needed. Numerous drugs already approved use, subsequently, there good understanding their safety profiles side effects, making them easier fast-track clinical studies patients. Here, we present data on antiviral activity against SARS-CoV-2 that also inhibit SARS-CoV Middle East (MERS-CoV). We found 17 these non-cytotoxic concentrations. directly followed up seven demonstrate all capable inhibiting infectious production. Moreover, evaluated two these, chloroquine chlorpromazine,

Language: Английский

---

Impact of hematologic malignancy and type of cancer therapy on COVID-19 severity and mortality: lessons from a large population-based registry study

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Oct. 8, 2020

Abstract Background Patients with cancer have been shown to a higher risk of clinical severity and mortality compared non-cancer patients COVID-19. hematologic malignancies typically are known levels immunosuppression may develop more severe respiratory viral infections than solid tumors. Data on COVID-19 in limited. Here we characterize disease evaluate potential prognostic factors for mortality. Methods In this population-based registry study, collected de-identified data characteristics, treatment outcomes adult confirmed acute syndrome coronavirus-2 (SARS-CoV-2) infection within the Madrid region Spain. Our case series included all admitted 22 regional health service hospitals 5 private healthcare centers between February 28 May 25, 2020. The primary study outcome was all-cause We assessed association using Cox regression analyses adjusted age, sex, comorbidities, malignancy recent active therapy. Results Of 833 reported, 697 were analyses. Median age 72 years (IQR 60–79), 413 (60%) male 479 (69%) 218 (31%) had lymphoid myeloid malignancies, respectively. Clinical severe/critical 429 (62%) patients. At cutoff, 230 (33%) died. Age ≥ 60 (hazard ratios 3.17–10.1 vs < 50 years), > 2 comorbidities (1.41 ≤ 2), leukemia (2.22 non-Hodgkin lymphoma) antineoplastic monoclonal antibodies (2·02) associated increased mortality; conventional chemotherapy showed borderline significance (1.50 no therapy). Conversely, Ph-negative myeloproliferative neoplasms (0.33) hypomethylating agents (0.47) lower Overall, 574 (82%) received antiviral Mortality therapy any combination (2.20). Conclusions COVID-19, type hematological Further studies long-term follow-up required validate these criteria stratification.

Language: Английский

---

Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: July 10, 2020

The rapidly spreading, highly contagious and pathogenic SARS-coronavirus 2 (SARS-CoV-2) associated Coronavirus Disease 2019 (COVID-19) has been declared as a pandemic by the World Health Organization (WHO). novel SARS-CoV-2 enters host cell binding of viral surface spike glycoprotein (S-protein) to cellular angiotensin converting enzyme (ACE2) receptor. virus specific molecular interaction with represents promising therapeutic target for identifying antiviral drugs. repurposing drugs can provide rapid potential cure towards exponentially expanding COVID-19. Thereto, high throughput virtual screening approach was used investigate FDA approved LOPAC library against both S-RBD ACE2 Primary identified few targets, which were further analysed in details their energy, modes through docking, dynamics simulations. Evidently, GR 127935 hydrochloride hydrate, GNF-5, RS504393, TNP eptifibatide acetate found motifs Additionally, KT203, BMS195614, KT185, RS504393 GSK1838705A bind at receptor site on S-protein. These drug molecules may effectively assist controlling spread not only potentially inhibiting entry step but also anti-inflammatory agents could impart relief lung inflammation. Timely identification determination an effective combat tranquilize COVID-19 global crisis is utmost need hour. Further, prompt vivo testing validate anti-SARS-CoV-2 inhibition efficiency these save lives justified.

Language: Английский

---

Potential of Flavonoid-Inspired Phytomedicines against COVID-19

Molecules, Journal Year: 2020, Volume and Issue: 25(11), P. 2707 - 2707

Published: June 11, 2020

Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these molecules can bind high affinity to the spike protein, helicase, protease sites ACE2 receptor by severe acute respiratory syndrome 2 infect cells cause COVID-19. Meanwhile, vitro of caflanone inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1β, IL-6, IL-8, Mip-1α, TNF-α), PI4Kiiiβ well AXL-2, which facilitates mother-to-fetus transmission coronavirus. The use smart drug delivery technologies like nanoparticle drones loaded overcome bioavailability limitations improve therapeutic efficacy discussed.

Language: Английский

---

Repurposing of Kinase Inhibitors for Treatment of COVID-19

Pharmaceutical Research, Journal Year: 2020, Volume and Issue: 37(9)

Published: Aug. 10, 2020

Language: Английский

---

COVID-19-driven endothelial damage: complement, HIF-1, and ABL2 are potential pathways of damage and targets for cure

Annals of Hematology, Journal Year: 2020, Volume and Issue: 99(8), P. 1701 - 1707

Published: June 24, 2020

COVID-19 pandemia is a major health emergency causing hundreds of deaths worldwide. The high reported morbidity has been related to hypoxia and inflammation leading endothelial dysfunction aberrant coagulation in small large vessels. This review addresses some the pathways derangement, such as complement, HIF-1α, ABL tyrosine kinases. also highlights potential targets for prevention therapy COVID-19-related organ damage discusses role marketed drugs, eculizumab imatinib, suitable candidates clinical trials.

Language: Английский

---

Identification of Candidate COVID-19 Therapeutics using hPSC-derived Lung Organoids

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: May 5, 2020

Summary Paragraph The SARS-CoV-2 virus has caused already over 3.5 million COVID-19 cases and 250,000 deaths globally. There is an urgent need to create novel models study using human disease-relevant cells understand key features of biology facilitate drug screening. As primary infection respiratory-based, we developed a lung organoid model pluripotent stem (hPSCs) that could be adapted for screens. organoids, particularly aveolar type II cells, express ACE2 are permissive infection. Transcriptomic analysis following revealed robust induction chemokines cytokines with little I/III interferon signaling, similar observed amongst pulmonary infections. We performed high throughput screen hPSC-derived organoids identified FDA-approved candidates, including imatinib mycophenolic acid, as inhibitors entry. Pre- or post-treatment these drugs at physiologically relevant levels decreased organoids. Together, data demonstrate infected by can disease provide valuable resource might repurposed should considered clinical trials.

Language: Английский

---

Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: March 27, 2020

Abstract SARS-CoV-2 emerged in China at the end of 2019 and has rapidly become a pandemic with roughly 2.7 million recorded COVID-19 cases greater than 189,000 deaths by April 23rd, 2020 ( www.WHO.org ). There are no FDA approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments limited to supportive therapies off-label use drugs. Rapid development human testing potential is greatly needed. A quick way test compounds antiviral activity through drug repurposing. Numerous drugs already subsequently there good understanding their safety profiles side effects, making them easier fast-track clinical studies patients. Here, we present data on 20 against that also inhibit SARS-CoV MERS-CoV. We found 17 these range IC50 values non-cytotoxic concentrations. directly follow up seven demonstrate all capable inhibiting infectious production. Moreover, have evaluated two these, chloroquine chlorpromazine, vivo using mouse-adapted model both protect mice from disease.

Language: Английский

---