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1.
Medical archives (Sarajevo, Bosnia and Herzegovina) ; 76(1):62-65, 2022.
Article in English | EuropePMC | ID: covidwho-1787014

ABSTRACT

Background: Thrombosis plays a crucial role in the morbidity and mortality of coronavirus disease-19 (COVID-19). About one-third of COVID-19 patients experience a thrombotic event, most commonly pulmonary embolism. Based on published data, the mechanism of thrombosis in COVID-19 patients seems to be multi-factorial. Methods: In this article, we reviewed the publsihed data concerning with thrombosis in COVID-19 and summarized the predisposing factors and the mechanisms behind COVID-19 related thrombosis. Results: Inflammatory response to SARS-CoV-2 and the consequent hyperviscosity thought to cause endothelial damage and initiate coagulation. Furthermore, inflammation promotes platelet activation and exerts a pathogenic effect on endothelial cells. The presence of anticardiolipin and anti–β2-glycoprotein antibodies in some patients with COVID-19 suggests that SARS-CoV-2, like many other viral infections, induces the formation of antiphospholipid antibodies, which provoke hypercoagulability. Thrombophilic mutations, mainly factor V Leiden and prothrombin G20201A mutations, can be a contributing factor in the development of thrombosis in COVID-19 patients, and they are associated with increased disease severity and pulmonary embolism. However, the research concerning with the association of thrombophilic mutations with COVID-19 related thrombosis showed conflict results. Conclusion: The mechanism of thrombosis in COVID-19 patients seems to be multifactorial. Endothelial damage, antiphospholipid antibodies, inflammation, hyperviscosity, and thrombophilic mutations are the main factors that predispose COVID-19 patients to. thrombosis.

2.
Comput Biol Med ; 145: 105478, 2022 Apr 07.
Article in English | MEDLINE | ID: covidwho-1778062

ABSTRACT

Finding a potent inhibitor to the pandemic SARS-CoV-2 is indispensable nowadays. Currently, in-silico methods work as expeditious investigators to screen drugs for possible repurposing or design new ones. Targeting one of the possible SARS-CoV-2 attachment and entry receptors, Glucose-regulated protein 78 (GRP78), is an approach of major interest. Recently, GRP78 was reported as a recognized representative in recognition of the latest variants of SARS-CoV-2. In this work, molecular docking and molecular dynamics simulations were performed on the host cell receptor GRP78. With its many terpenoid compounds, Chaga mushroom was tested as a potential therapeutic against the SARS-CoV-2 receptor, GRP78. Results revealed low binding energies (high affinities) toward the GRP78 substrate-binding domain ß (SBDß) of Chaga mushroom terpenoids. Even the highly specific cyclic peptide Pep42, which selectively targeted GRP78 over cancer cells in vivo, showed lower binding affinity against GRP78 SBDß compared to the binding affinities of terpenoids. These are auspicious results that need to be tested experimentally. Intriguingly, terpenoids work as a double sword as they can be used to interfere with VUI 202,012/01, 501.V2, and B.1.1.248 variants of SARS-CoV-2 spike recognition.

3.
Comput Biol Med ; 145: 105452, 2022 Mar 26.
Article in English | MEDLINE | ID: covidwho-1757244

ABSTRACT

SARS-CoV-2, a rapidly spreading new strain of human coronavirus, has affected almost all the countries around the world. The lack of specific drugs against SARS-CoV-2 is a significant hurdle towards the successful treatment of COVID-19. Thus, there is an urgent need to boost up research for the development of effective therapeutics against COVID-19. In the current study, we investigated the efficacy of 81 medicinal plant-based bioactive compounds against SARS-CoV-2 Mpro by using various in silico techniques. The interaction affinities of polyphenolic compounds towards SARS-CoV-2 Mpro was assessed via intramolecular (by Quantum Mechanic), intermolecular (by Molecular Docking), and spatial (by Molecular Dynamic) simulations. Our obtained result demonstrate that Hesperidin, rutin, diosmin, and apiin are most effective compounds agents against SARS-CoV-2 Mpro as compared to Nelfinavir (positive control). This study will hopefully pave a way for advanced experimental research to evaluate the in vitro and in vivo efficacy of these compounds for the treatment of COVID-19.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312904

ABSTRACT

Coronaviruses have been circulating between animals and humans repeatedly. A novel human coronavirus, named COVID-19, has recently emerged in Hubei Province, China. Within the first two months, more than 2200 deaths have been confirmed, and there have been more than 79,000 hospitalized patients, mainly in China. Understanding the virus mode of host cell recognition may help to fight the disease and save lives. The spike protein of coronaviruses is the main driving force for host cell recognition. In this study, the COVID-19 corona viral spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined molecular modeling docking and structural bioinformatics. The cyclic peptide Pep42 (CTVALPGGYVRVC) was reported earlier to be the docking platform of GRP78 in cancer cells. The COVID-19 spike protein is modeled using its counterpart, the SARS spike. Sequence and structural alignments show that four regions, in addition to its cyclic nature (the S-S bond), have sequence and physicochemical similarities to the cyclic Pep42. Protein-protein docking was performed to test the four regions of the spike that fit tightly in the GRP78 Substrate Binding Domain β (SBDβ). The docking pose revealed the involvement of the SBDβ of GRP78 and the receptor-binding domain of the coronavirus spike protein in recognition of the host cell receptor. We reveal that the binding is more favorable between regions III (C391-C525) and IV (C480-C488) of the spike protein model and GRP78. Region IV is the main driving force for GRP78 binding with the predicted binding affinity of -9.8 kcal/mol. These nine residues (region IV) of the spike can be used to develop therapeutics specific against COVID-19.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311805

ABSTRACT

Targeting viral cell entry proteins is an emerging therapeutic strategy for inhibiting the first stage of SARS-CoV-2 infection. In this study, 106 bioactive terpenoids from African medicinal plants were screened through molecular docking analysis against human angiotensin-converting enzyme 2 ( h ACE2), human transmembrane protease serine 2 (TMPRSS2) and the S proteins of SARS-CoV-2, SARS-CoV and MERS-CoV. In silico ADMET and drug-likeness prediction, molecular dynamics simulation (MDS), binding free energy calculations and clustering analysis of MDS trajectories were performed on the top docked compounds to respective targets. The results revealed eight terpenoids with high binding tendencies to the catalytic residues of different targets. Pentacyclic terpenoids: 24-methylene cycloartenol and isoiguesterin interacted with the h ACE2 binding hotspots for the SARS-CoV-2 Spike protein. 11-hydroxy-2 - (3,4-dihydroxybenzoyloxy) abieta -5,7,9 (11),13-tetraene-12-one, 11-hydroxy-2 -(4-hydroxybenzoyloxy)-abieta- 5,7,9(11),13-tetraene-12-one and other abietane diterpenes interacted strongly with the S1-specificy pocket of TMPRSS2. 3-benzoylhosloppone and cucurbitacin interacted with the RBD and S2 subunit of SARS-CoV-2 spike protein respectively. The predicted druggable and ADMET favourable terpenoids formed structurally stable complexes in the simulated dynamics environment. These terpenoids provides core structure that can be exploited for further lead optimization to design drugs against SARS-CoV-2 cell mediated entry, subject to further in vitro and in vivo studies.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311804

ABSTRACT

The high morbidity and mortality rate of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection arises majorly from the Acute Respiratory Distress Syndrome and “cytokine storm” syndrome, which is sustained by an aberrant systemic inflammatory response and elevated pro-inflammatory cytokines. Thus, phytocompounds with broad-spectrum anti-inflammatory activity that target multiple SARS-CoV-2 proteins will enhance the development of effective drugs against the disease. In this study, an in-house library of 106 steriodal plant-derived pregnanes (PDPs) was docked in the active regions of human glucocorticoid receptors ( h GRs) in a comparative molecular docking analysis. Based on the minimal binding energy and a comparative dexamethason binding mode analysis, a list of top twenty ranked PDPs docked in the agonist conformation of h GR, with binding energies ranging between -9.8 and -11.2 Kcal/mol, was obtained and analyzed for interactions with the human Janus kinases 1 and Interleukins-6 and SARS-CoV-2 3-chymotrypsin-like protease, Papain-like protease and RNA-dependent RNA polymerase. For each target protein, the top three ranked PDPs were selected. Eight PDPs (bregenin, hirundigenin, anhydroholantogenin, atratogenin A, atratogenin B, glaucogenin A, glaucogenin C and glaucogenin D) with high binding tendencies to the catalytic residues of multiple targets were identified. A high degree of structural stability was observed from the 100 ns molecular dynamics simulation analyses of glaucogenin C and hirundigenin complexes of h GR. The selected top-eight ranked PDPs demonstrated favourable druggable and in silico ADMET properties. Thus, the therapeutic potentials of glaucogenin C and hirundigenin can be explored for further in vitro and in vivo studies.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311803

ABSTRACT

An in-house library of 173 phytocompound structures from Vernonia amygdalina and Occinum gratissimum was screened against the active region of 3-Chymotrypsin-Like Protease (3CL pro ) of SARS-CoV-2 in silico. Based on docking scores and reference inhibitors, a hit- list of 21 phytocompounds, with binding energies ranging from − 7.2 to -8.0 kcal/mol, was initially generated. Further docking against the 3CL pro of related coronaviruses (SARS-CoV and MERS-CoV), docking to 5 different representative conformations generated from the cluster analysis of SARS-CoV-2 3CL pro molecular dynamics simulation (MDS) trajectories, and in silico drug-likeness analyses, revealed two drug-like terpenoid structures as promising non-covalent inhibitors of SARS-CoV-2 3CL Pro viz: neoandrographolide and vernolide. These terpenoid structures are accommodated within the substrate-binding pocket, and interacted with the catalytic dyad, the oxyanion loop (residues 138–145), and the S1/S2 subsites of the enzyme active site. With the aid of an array of hydrogen bonds and hydrophobic interactions with residues 142–145, these phytocompounds may stabilize the conformation of the flexible oxyanion loop;and thereby interfere with the tetrahedral oxyanion intermediate formation during proteolytic cleavage. Molecular dynamics simulation and binding free energy calculation further revealed that the terpenoid-enzyme complexes exhibit strong interactions and structural stability, which could be adapted for experimental models.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-309957

ABSTRACT

New SARS-CoV-2 variants started in the UK and South Africa in December 2020 and currently spreading worldwide during the last few days. Additionally, another more recent variant sparked in Brazil (B.1.1.248 lineage) this month. The new variant 501.V2 (South African) bears three mutations in the receptor-binding domain (RBD) of the spike glycoprotein, K417N, E484K, and N501Y, while the Brazilian B.1.1.248 lineage have 12 mutations. The N501Y mutation is found in South African and Brazilian variants and is also shared with the UK variant VOC-202012/01 (1). This mutation may affect the host-cell receptor ACE2 (angiotensin-converting enzyme 2) recognition (2). Despite its presence in the ACE2 binding surface, we showed that the N501Y mutant shows a remarkable increase in binding of the ACE2-RBD complex to the host-cell surface Glucose Regulated Protein 78 (CS-GRP78) (3). On the other hand, the E484K is found in the spike RBD's binding motif that we reported earlier to be recognized by cell-surface GRP78 (C480-C488 region of the spike) (4). In this study, we simulate the complex ACE2-SARS-CoV-2 spike RBD system in which the RBD is in the wildtype and mutated (K417N, E484K, and N501Y) isoforms. Additionally, the CS-GRP78 association with the ACE2-SARS-CoV-2 spike RBD complex (ACE2-RBD) is modeled at the presence of these mutant variants of the viral spike.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-309956

ABSTRACT

New SARS-CoV-2 variant VUI 202012/01 started in the UK and currently spreading in Europe and Australia during the last few days. The new variant bears about nine mutations in the spike protein (Δ69-70, Δ145, N501Y, A570D, D614G, P681H, T716I, S982A, and D1118H). The N501Y lies in the receptor-binding domain (RBD) of the spike and interacts with the host-cell receptor ACE2 responsible for viral recognition and entry. We tried to simulate the system of ACE2-SARS-CoV-2 spike RBD in the wildtype and mutated isoform of the RBD (N501Y). Additionally, the GRP78 association with the ACE2-SARS-CoV-2 spike RBD is modeled at the presence of this mutant variant of the viral spike.

10.
RSC Adv ; 12(5): 2741-2750, 2022 Jan 18.
Article in English | MEDLINE | ID: covidwho-1649923

ABSTRACT

According to the World Health Organization (WHO), SARS-CoV-2 is responsible for more than 5 M deaths and is reported in 223 countries infecting 250+ M people. Despite the current vaccination momentum, thousands of people die every day by COVID-19. Suggesting possible blockers of the viral RNA-dependent RNA polymerase is highly needed for potential effective therapeutics against SARS-CoV-2. This study utilizes combined molecular dynamics simulation and molecular docking to test novel guanosine derivatives against SARS-CoV-2 RdRp. Results reveal the binding potency of nineteen guanosine derivatives against SARS-CoV-2 solved structures. The bulky moieties (hydroxyl or fluorated phenyl moieties) added to the 2' position of the ribose ring positively impacted the binding affinity to RdRp. The current in silico study represents a one-step-ahead for suggesting new possible blockers of SARS-CoV-2 RdRp that are yet to be verified in the wet lab. It offers new potential binders or blockers of RdRp that bind to the protein active site tighter than remdesivir. The latter was approved by the food and drug administration (FDA) for emergency use against COVID-19 last year.

12.
Molecules ; 26(21)2021 Oct 26.
Article in English | MEDLINE | ID: covidwho-1488676

ABSTRACT

A novel human coronavirus prompted considerable worry at the end of the year 2019. Now, it represents a significant global health and economic burden. The newly emerged coronavirus disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the primary reason for the COVID-19 global pandemic. According to recent global figures, COVID-19 has caused approximately 243.3 million illnesses and 4.9 million deaths. Several human cell receptors are involved in the virus identification of the host cells and entering them. Hence, understanding how the virus binds to host-cell receptors is crucial for developing antiviral treatments and vaccines. The current work aimed to determine the multiple host-cell receptors that bind with SARS-CoV-2 and other human coronaviruses for the purpose of cell entry. Extensive research is needed using neutralizing antibodies, natural chemicals, and therapeutic peptides to target those host-cell receptors in extremely susceptible individuals. More research is needed to map SARS-CoV-2 cell entry pathways in order to identify potential viral inhibitors.


Subject(s)
Coronavirus/metabolism , Host Microbial Interactions/physiology , Receptors, Coronavirus/metabolism , Antibodies, Neutralizing , Antiviral Agents/pharmacology , COVID-19 , Coronavirus/pathogenicity , Humans , Receptors, Coronavirus/physiology , Receptors, Virus/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects
13.
Am J Trop Med Hyg ; 106(3): 886-890, 2021 09 10.
Article in English | MEDLINE | ID: covidwho-1468605

ABSTRACT

To date, no antiviral therapy has shown proven clinical effectiveness in treating patients with COVID-19. We assessed the efficacy of remdesivir in hospitalized Egyptian patients with COVID-19. Patients were randomly assigned at a 1:1 ratio to receive either remdesivir (200 mg on the first day followed by 100 mg daily for the next 9 days intravenously infused over 30-60 minutes) in addition to standard care or standard care alone. The primary outcomes were the length of hospital stay and mortality rate. The need for mechanical ventilation was assessed as a secondary outcome. Two hundred patients (100 in each group) completed the study and were included in the final analysis. The remdesivir group showed a significantly lower median duration of hospital stay (10 days) than the control group (16 days; P < 0.001). Eleven of the patients in the remdesivir group needed mechanical ventilation compared with eight patients in the control group (P = 0.469). The mortality rate was comparable between the two groups (P = 0.602). Mortality was significantly associated with older age, elevated C-reactive protein levels, elevated D-dimer, and the need for mechanical ventilation (P = 0.039, 0.003, 0.001, and < 0.001 respectively). Remdesivir had a positive influence on length of hospital stay, but it had no mortality benefit in Egyptian patients with COVID-19. Its use, in addition to standard care including dexamethasone, should be considered, particularly in low- and middle-income countries when other effective options are scarce.


Subject(s)
COVID-19 , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , SARS-CoV-2 , Treatment Outcome
14.
Computers, Materials, & Continua ; 70(2):2507-2524, 2022.
Article in English | ProQuest Central | ID: covidwho-1449535

ABSTRACT

Social networking sites in the most modernized world are flooded with large data volumes. Extracting the sentiment polarity of important aspects is necessary;as it helps to determine people’s opinions through what they write. The Coronavirus pandemic has invaded the world and been given a mention in the social media on a large scale. In a very short period of time, tweets indicate unpredicted increase of coronavirus. They reflect people’s opinions and thoughts with regard to coronavirus and its impact on society. The research community has been interested in discovering the hidden relationships from short texts such as Twitter and Weiboa;due to their shortness and sparsity. In this paper, a hierarchical twitter sentiment model (HTSM) is proposed to show people’s opinions in short texts. The proposed HTSM has two main features as follows: constructing a hierarchical tree of important aspects from short texts without a predefined hierarchy depth and width, as well as analyzing the extracted opinions to discover the sentiment polarity on those important aspects by applying a valence aware dictionary for sentiment reasoner (VADER) sentiment analysis. The tweets for each extracted important aspect can be categorized as follows: strongly positive, positive, neutral, strongly negative, or negative. The quality of the proposed model is validated by applying it to a popular product and a widespread topic. The results show that the proposed model outperforms the state-of-the-art methods used in analyzing people’s opinions in short text effectively.

15.
Arab J Chem ; 14(10): 103385, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1356130

ABSTRACT

Background: COVID-19 is an ongoing viral pandemic produced by SARS-CoV-2. In light of in vitro efficacy, several medications were repurposed for its management. During clinical use, many of these medications produced inconsistent results or had varying limitations. Objective: The purpose of this literature review is to explain the variable efficacy or limitations of Lopinavir/Ritonavir, Remdesivir, Hydroxychloroquine, and Favipiravir in clinical settings. Method: A study of the literature on the pharmacodynamics (PD), pharmacokinetics (PK), safety profile, and clinical trials through academic databases using relevant search terms. Results & discussion: The efficacy of an antiviral drug against COVID-19 is associated with its ability to achieve therapeutic concentration in the lung and intestinal tissues. This efficacy depends on the PK properties, particularly protein binding, volume of distribution, and half-life. The PK and PD of the model drugs need to be integrated to predict their limitations. Conclusion: Current antiviral drugs have varying pharmacological constraints that may associate with limited efficacy, especially in severe COVID-19 patients, or safety concerns.

16.
J Genet Eng Biotechnol ; 19(1): 113, 2021 Aug 05.
Article in English | MEDLINE | ID: covidwho-1344136

ABSTRACT

BACKGROUND: Targeting viral cell entry proteins is an emerging therapeutic strategy for inhibiting the first stage of SARS-CoV-2 infection. In this study, 106 bioactive terpenoids from African medicinal plants were screened through molecular docking analysis against human angiotensin-converting enzyme 2 (hACE2), human transmembrane protease serine 2 (TMPRSS2), and the spike (S) proteins of SARS-CoV-2, SARS-CoV, and MERS-CoV. In silico absorption-distribution-metabolism-excretion-toxicity (ADMET) and drug-likeness prediction, molecular dynamics (MD) simulation, binding free energy calculations, and clustering analysis of MD simulation trajectories were performed on the top docked terpenoids to respective protein targets. RESULTS: The results revealed eight terpenoids with high binding tendencies to the catalytic residues of different targets. Two pentacyclic terpenoids (24-methylene cycloartenol and isoiguesteri) interacted with the hACE2 binding hotspots for the SARS-CoV-2 spike protein, while the abietane diterpenes were found accommodated within the S1-specificity pocket, interacting strongly with the active site residues TMPRSS2. 3-benzoylhosloppone and cucurbitacin interacted with the RBD and S2 subunit of SARS-CoV-2 spike protein respectively. These interactions were preserved in a simulated dynamic environment, thereby, demonstrating high structural stability. The MM-GBSA binding free energy calculations corroborated the docking interactions. The top docked terpenoids showed favorable drug-likeness and ADMET properties over a wide range of molecular descriptors. CONCLUSION: The identified terpenoids from this study provides core structure that can be exploited for further lead optimization to design drugs against SARS-CoV-2 cell-mediated entry proteins. They are therefore recommended for further in vitro and in vivo studies towards developing entry inhibitors against the ongoing COVID-19 pandemic.

17.
Comput Biol Med ; 136: 104671, 2021 09.
Article in English | MEDLINE | ID: covidwho-1322055

ABSTRACT

Antiviral culinary plants are potential bioresources for preventive nutraceuticals and/or antiviral drugs in COVID-19. Structure-based virtual screening was undertaken to screen 173 compounds previously reported from Vernonia amygdalina and Occinum gratissimum for direct interaction with the active site of the 3-Chymotrypsin-Like Protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on docking scores and comparison with reference inhibitors, a hit-list of 10 top phytocompounds was defined, which also had strong interactions with the catalytic centre of 3CLpro from three related strains of coronavirus (SARS-CoV, MERS-CoV, HKU4). Among these, six compounds (neoandrographolide, vernolide, isorhamnetin, chicoric acid, luteolin, and myricetin) exhibited the highest binding tendencies to the equilibrated conformers of SARS-CoV-2 3CLpro in an in-depth docking analysis to 5 different representative conformations from the cluster analysis of the molecular dynamics simulation (MDS) trajectories of the protein. In silico drug-likeness analyses revealed two drug-like terpenoids viz: neoandrographolide and vernolide as promising inhibitors of SARS-CoV-2 3CLpro. These structures were accommodated within the substrate-binding pocket; and interacted with the catalytic dyad (Cys145 and His41), the oxyanion loop (residues 138-145), and the S1/S2 sub-sites of the enzyme active site through the formation of an array of hydrogen bonds and hydrophobic interactions. Molecular dynamics simulation and binding free energy calculation revealed that the terpenoid-enzyme complexes exhibit strong interactions and structural stability. Therefore, these compounds may stabilize the conformation of the flexible oxyanion loop; and thereby interfere with the tetrahedral oxyanion intermediate formation during the proteolytic activity of the enzyme.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus 3C Proteases/antagonists & inhibitors , Ocimum/chemistry , Phytochemicals/pharmacology , SARS-CoV-2/drug effects , Vernonia , COVID-19 , Chymases , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors , Vernonia/chemistry
18.
Preprint in English | medRxiv | ID: ppmedrxiv-21257942

ABSTRACT

Alpha (B.1.1.7) SARS-COV-2 variant was detected in September 2020 in minks and humans in Denmark and UK. This variant has several mutations in the spike region (S) which could increase the transmissibility of the virus 43-90% over previously circulating variants. The National Center for Disease Control (NCDC) announced on 24th February 2021 a 25% frequency of B.1.1.7 strain in Libya using a reverse-transcriptase quantitative PCR assay. This assay relies on the specific identification of the H69-V70 deletion in S gene which causes its failure of amplification (SGTF). This deletion is not specific for B.1.1.7; but is also characteristic of two other SARS-COV-2 variants. This study aimed to estimate the frequency of B.1.1.7 and identify other variants circulating in Libya in February 2021. We performed whole genome sequencing of 67 positive SARS-COV-2 samples collected on 25th February 2021 in Libya which were also tested by RT-qPCR for SGTF. Our results showed that 55% of samples had mutations specific to B.1.525 strain and only [~]3% of samples belonged to B.1.1.7. These findings suggested that B.1.525 was spreading widely in Libya. The use of such RT-qPCR assay although useful to track some variants, it cannot discriminate between variants with H69-V70 deletion. RT-qPCR assays could be multiplexed to identify multiple variants and screen samples prior to sequencing. We emphasize on the need for providing whole-genome sequencing to the main COVID-19 diagnostic laboratories in Libya as well as establishing international collaboration for building capacity and advancing research in this time of the pandemic.

19.
Pharmacol Rep ; 73(6): 1754-1764, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1283833

ABSTRACT

BACKGROUND: SARS-CoV-2 is a newly emerged human coronavirus that severely affected human health and the economy. The viral RNA-dependent RNA polymerase (RdRp) is a crucial protein target to stop virus replication. The adenosine derivative, remdesivir, was authorized for emergency use 10 months ago by the United States FDA against COVID-19 despite its doubtful efficacy against SARS-CoV-2. METHODS: A dozen modifications based on remdesivir are tested against SARS-CoV-2 RdRp using combined molecular docking and dynamics simulation in this work. RESULTS: The results reveal a better binding affinity of 11 modifications compared to remdesivir. Compounds 8, 9, 10, and 11 show the best binding affinities against SARS-CoV-2 RdRp conformations gathered during 100 ns of the Molecular Dynamics Simulation (MDS) run (- 8.13 ± 0.45 kcal/mol, - 8.09 ± 0.67 kcal/mol, - 8.09 ± 0.64 kcal/mol, and - 8.07 ± 0.73 kcal/mol, respectively). CONCLUSIONS: The present study suggests these four compounds as potential SARS-CoV-2 RdRp inhibitors, which need to be validated experimentally.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Adenosine/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/chemistry , Coronavirus RNA-Dependent RNA Polymerase/antagonists & inhibitors , Drug Design , Adenosine Monophosphate/chemistry , Alanine/chemistry , Binding Sites , COVID-19 , Computer Simulation , Coronavirus RNA-Dependent RNA Polymerase/chemistry , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Molecular Structure , SARS-CoV-2/pathogenicity
20.
Br J Haematol ; 194(3): 530-536, 2021 08.
Article in English | MEDLINE | ID: covidwho-1270823

ABSTRACT

COVID-19, caused by SARS-CoV-2, is a contagious life-threatening viral disease that has killed more than three million people worldwide to date. Attempts have been made to identify biomarker(s) to stratify disease severity and improve treatment and resource allocation. Patients with SARS-COV-2 infection manifest with a higher inflammatory response and platelet hyperreactivity; this raises the question of the role of thrombopoiesis in COVID-19 infection. Immature platelet fraction (IPF, %) and immature platelet counts (IPC, ×109 /l) can be used to assess thrombopoiesis. This study investigates whether the level of thrombopoiesis correlates with COVID-19 severity. A large cohort of 678 well-characterized COVID-19 patients was analyzed, including 658 (97%) hospitalized and 139 (21%) admitted to the intensive care unit (ICU). Elevated percentage IPF at presentation was predictive of length of hospitalization (P < 0·01) and ICU admission (P < 0·05). Additionally, percentage IPF at the peak was significantly higher among ICU patients than non-ICU patients (6·9 ± 5·1 vs 5·3 ± 8·4, P < 0·01) and among deceased patients than recovered patients (7·9 ± 6·3 vs 5·4 ± 7·8, P < 0·01). Furthermore, IPC at the peak was significantly higher among ICU patients than non-ICU patients (18·5 ± 16·2 vs. 13·2 ± 8·3, P < 0·05) and among patients on a ventilator than those not (22·1 ± 20·1 vs.13·4 ± 8·4, P < 0·05). Our study demonstrated that elevated initial and peak values of percentage IPF and IPC might serve as prognostic biomarkers for COVID-19 progression to severe conditions.


Subject(s)
Blood Platelets/pathology , COVID-19/pathology , Thrombopoiesis , Aged , Blood Platelets/cytology , COVID-19/blood , COVID-19/mortality , Female , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Platelet Count , SARS-CoV-2/isolation & purification , Severity of Illness Index
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