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1.
Acta Biotheor ; 70(2): 16, 2022 May 19.
Article in English | MEDLINE | ID: covidwho-1850367

ABSTRACT

The COVID-19 pandemic has resulted in more than 524 million cases and 6 million deaths worldwide. Various drug interventions targeting multiple stages of COVID-19 pathogenesis can significantly reduce infection-related mortality. The current within-host mathematical modeling study addresses the optimal drug regimen and efficacy of combination therapies in the treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Interferon (INF) and Lopinavir/Ritonavir. It is concluded that these drugs, when administered singly or in combination, reduce the number of infected cells and viral load. Four scenarios dealing with the administration of a single drug, two drugs, three drugs and all four are discussed. In all these scenarios, the optimal drug regimen is proposed based on two methods. In the first method, these medical interventions are modeled as control interventions and a corresponding objective function and optimal control problem are formulated. In this framework, the optimal drug regimen is derived. Later, using the comparative effectiveness method, the optimal drug regimen is derived based on the basic reproduction number and viral load. The average number of infected cells and viral load decreased the most when all four drugs were used together. On the other hand, the average number of susceptible cells decreased the most when Arbidol was administered alone. The basic reproduction number and viral load decreased the most when all four interventions were used together, confirming the previously obtained finding of the optimal control problem. The results of this study can help physicians make decisions about the treatment of the life-threatening COVID-19 infection.


Subject(s)
COVID-19 , Animals , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Pandemics , Pharmaceutical Preparations , SARS-CoV-2
2.
Gene Rep ; 27: 101619, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1819494

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a remarkably contagious and pathogenic viral infection arising from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first appeared in Wuhan, China. For the time being, COVID-19 is not treated with a specific therapy. The Food and Drug Administration (FDA) has approved Remdesivir as the first drug to treat COVID-19. However, many other therapeutic approaches are being investigated as possible treatments for COVID-19. As part of this review, we discussed the development of various drugs, their mechanism of action, and how they might be applied to different cases of COVID-19 patients. Furthermore, this review highlights an update in the emergence of new prophylactic or therapeutic vaccines against COVID-19. In addition to FDA or The World Health Organization (WHO) approved vaccines, we intended to incorporate the latest published data from phase III trials about different COVID-19 vaccines and provide clinical data released on the networks or peer-review journals.

3.
Nanomaterials (Basel) ; 12(8)2022 Apr 10.
Article in English | MEDLINE | ID: covidwho-1810053

ABSTRACT

Deep eutectic solvents are a new generation of green solvents composed of hydrogen bond acceptors and donors. However, when used as extractants in liquid-liquid separation, they are difficult to recycle and easy to lose. In order to solve these problems, herein, immobilized hydrogen bond acceptor adsorbent material was prepared for the separation and enrichment of antiviral drug arbidol from seven kinds of environmental water samples by in situ formation of hydrophobic deep eutectic solvents. The structure, morphology and thermal stability of the adsorbents were characterized, the separation and enrichment conditions for the targeted analyte were optimized, and the adsorption thermodynamics and kinetics were investigated. It was found that the adsorbent material could effectively enrich trace arbidol with the recovery more than 95% at the concentration above 7.5 ng/mL, and the enrichment factor was as high as 634.7. Coexisting substances, such as NaCl, KCl, CaCl2 and MgCl2, did not interfere with the adsorption of arbidol, even if their concentration was high, up to 1.0 mol/L, and the relative recovery for real samples was in the range from 92.5% to 100.3%. Furthermore, the immobilized hydrogen bond acceptor could be recycled and reused, and the recovery of arbidol was still above 95% after 12 adsorption-desorption cycles. The mechanism study demonstrates that the synergistic effect of hydrogen bonding and π-π stacking is the primary factor for the high adsorption efficiency.

4.
J Med Virol ; 94(4): 1513-1522, 2022 04.
Article in English | MEDLINE | ID: covidwho-1718397

ABSTRACT

OBJECTIVES: To systematically evaluate the efficacy and safety of arbidol and lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19) using a meta-analysis method. METHODS: The China Knowledge Network, VIP database, WanFang database PubMed database, Embase database, and Cochrane Library were searched for a collection of comparative studies on arbidol and lopinavir/ritonavir in the treatment of COVID-19. Meta-analysis was used to evaluate the efficacy and safety of Arbidol and lopinavir/ritonavir in the treatment of COVID-19. RESULTS: The results of the systematic review indicated that Arbidol had a higher positive-to-negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid on Day 7 (p = 0.03), a higher positive-to-negative conversion rate of SARS-CoV-2 nucleic acid on Day 14 (p = 0.006), a higher improvement rate of chest computed tomography on Day 14 (p = 0.02), a lower incidence of adverse reactions (p = 0.002) and lower rate of mortality (p = 0.007). There was no difference in the rate of cough disappearance on Day 14 (p = 0.24) or the rate of severe/critical illness (p = 0.07) between the two groups. CONCLUSIONS: Arbidol may be superior to lopinavir/ritonavir in the treatment of COVID-19. However, due to the small number of included studies and the number of patients, high-quality multicenter large-sample randomized double-blind controlled trials are still needed for verification.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Indoles/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Sulfides/therapeutic use , COVID-19/mortality , Drug Combinations , Humans , Indoles/adverse effects , Lopinavir/adverse effects , Ritonavir/adverse effects , SARS-CoV-2/drug effects , Sulfides/adverse effects , Treatment Outcome
5.
Asian Journal of Organic Chemistry ; 2022.
Article in English | Scopus | ID: covidwho-1700972

ABSTRACT

Sulfur-containing indoles are widely studied against different biological targets. Among several potential drug candidates, seven molecules of this class are in the current market and a few of them are either in pipeline or in different stages of clinical trials. Particularly, arylthioindoles or indolylarylsulfones (IAS) received great attention by medicinal chemists due to their pharmokinetic profiles and wide spectrum of biological activities like antiviral, anticancer, cardiovascular, and antibacterial properties. This review summarizes the developmental process, synthesis and structure activity relationship (SAR) around arylthioindole/indolylaryl sulfone scaffolds for antiviral/anti-HIV non-nucleoside reverse transcriptase inhibitor (NNRTIs) activities. It also offers perspective for further development of 3-indolylarylsulfones as an anti-viral agent including their potential against novel COVID-19 infection. © 2022 Wiley-VCH GmbH

6.
Journal of Cleaner Production ; : 130753, 2022.
Article in English | ScienceDirect | ID: covidwho-1665150

ABSTRACT

With the global spread of the COVID-19 pandemic, the water pollution caused by extensive production and application of COVID-19 related drugs has aroused growing attention. Herein, a novel biochar-supported red mud catalyst (RM-BC) containing abundant free hydroxyl groups was synthesized. The RM-BC activated persulfate process was firstly put forward to degrade COVID-19 related drugs, including arbidol (ARB), chloroquine phosphate, hydroxychloroquine sulfate, and acyclovir. Highly effective removal of these pharmaceuticals was achieved and even 100% of ARB was removed within 12 min at optimum conditions. Mechanism study indicated that SO4•− and HO• were the predominant radicals, and these radicals were responsible for the formation of DMPOX in electron spin resonance experiments. Fe species (Fe0 and Fe3O4) and oxygen-containing functional groups in RM-BC played crucial roles in the elimination of ARB. Effects of degradation conditions and several common water matrices were also investigated. Finally, the degradation products of ARB were identified by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and possible degradation pathways were proposed. This study demonstrated that RM-BC/PS system would have great potential for the removal of COVID-19 related drug residues in water by the catalyst synthesized from the solid waste.

7.
Current Nanoscience ; 17(6):844-852, 2021.
Article in English | Web of Science | ID: covidwho-1636811

ABSTRACT

The entire world is now in a state of caution since the outbreak of the COVID-19 pandemic. The overwhelmingly high spread and mortality rate due to the SARS-CoV-2 virus has not only made the headlines but also raised alarming concerns for the human community. Applications of nano-biotechnology, along with machine learning, have excellent potential in dealing with serious health issues, mainly in medical science. This review article aims to augment the multidimensional use of silver nanoparticles, especially in the fabrication of textiles and face masks, which could represent a new avenue for prevention. Furthermore, the disinfection of COVID-19, along with other pathogens using silver nanoparticles and machine learning could help in the risk assessment.

8.
Zhonghua Nei Ke Za Zhi ; 59(8): 605-609, 2020 Aug 01.
Article in Chinese | MEDLINE | ID: covidwho-1556260

ABSTRACT

Objective: To evaluate the efficacy and safety of lopinavir/ritonavir (LPV/r) and arbidol in treating patients with coronavirus disease 2019 (COVID-19) in the real world. Methods: The clinical data of 178 patients diagnosed with COVID-19 admitted to Guangzhou Eighth People's Hospital from January 20 to February 10, 2020 were retrospectively analyzed. According to patient's antiviral treatment regimens, 178 patients were divided into 4 groups including LPV/r group (59 patients), arbidol group (36 patients), LPV/r plus arbidol combination group (25 patients) and the supportive care group without any antiviral treatment (58 patients). The primary end point was the negative conversion time of nucleic acid of 2019 novel coronavirus (2019-nCoV) by pharyngeal swab. Results: The baseline parameters of 4 groups before treatment was comparable. The negative conversion time of viral nucleic acid was (10.20±3.49), (10.11±4.68), (10.86±4.74), (8.44±3.51) days in LPV/r group, arbidol group, combination group, and supportive care group respectively (F=2.556, P=0.058). There was also no significant difference in negative conversion rate of 2019-nCoV nucleic acid, the improvement of clinical symptoms, and the improvement of pulmonary infections by CT scan (P>0.05). However, a statistically significant difference was found in the changing rates from mild/moderate to severe/critical type at day 7 (χ(2)=9.311, P=0.017), which were 24%(6/25) in combination group, 16.7%(6/36) in arbidol group, 5.4%(3/56) in LPV/r group and 5.2%(3/58) in supportive care group. Moreover, the incidence of adverse reactions in three antiviral groups was significantly higher than that in supportive care group (χ(2)=14.875, P=0.002). Conclusions: Antiviral treatment including LPV/r or arbidol or combination does not shorten the negative conversion time of 2019-nCoV nucleic acid nor improve clinical symptoms. Moreover, these antiviral drugs cause more adverse reactions which should be paid careful attention during the treatment.


Subject(s)
COVID-19 , HIV Infections , COVID-19/drug therapy , HIV Infections/drug therapy , Humans , Indoles , Lopinavir/adverse effects , Retrospective Studies , Ritonavir/adverse effects , SARS-CoV-2
9.
Ann Palliat Med ; 10(10): 10626-10632, 2021 10.
Article in English | MEDLINE | ID: covidwho-1515697

ABSTRACT

BACKGROUND: The aim of this study was to determine whether Arbidol has a good antiviral effect on coronavirus disease 2019 (COVID-19). METHODS: A retrospective cohort study was performed in one of the treatment centers for COVID-19 patients in China from January 2020 to March 2020. The antiviral drug Arbidol (ARB) was administrated to some of the patients at 0.2 g tid po for 7 to 10 days. According to whether patients were given ARB, they were divided into 2 groups: the ARB group and the Non-ARB group. The primary outcome was the 14-day COVID-19 negativity rate. RESULTS: Of 146 patients, 140 were included. A total of 79 (56.4%) patients received ARB during hospitalization. In the overall cohort, the time of COVID-19 negativity in the ARB group compared with the Non-ARB group was 12.9 days versus 12.7 days (P=0.175; >0.05). The rates of 14-day COVID-19 negativity were 60.8% and 65.6% in the ARB and non-ARB groups, respectively (P=0.559; >0.05). Using an adjusted model, there were no obvious differences in the time of COVID-19 negativity and the rates of 14-day COVID-19 negativity (P>0.05). According to Kaplan-Meier analysis, the probabilities of 14-day COVID-19 negativity were similar in the 2 groups (log-rank P=0.130; >0.05). In a multivariate Cox analysis, the variables of age [hazard ratio (HR) 0.91, 95% confidence interval (CI): 0.83 to 0.99; P=0.039] and glucose (HR 0.90, 95% CI: 0.82 to 0.98; P=0.021) were independently associated with 14-day COVID-19 negativity. CONCLUSIONS: Our results suggest that there was no apparent favorable clinical response with ARB both in clinical symptoms and the 14-day COVID-19 negativity rate.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Cohort Studies , Humans , Indoles , Retrospective Studies
10.
Virol J ; 18(1): 142, 2021 07 08.
Article in English | MEDLINE | ID: covidwho-1496196

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the role of antiviral drugs in reducing the risk of developing severe illness in patients with moderate COVID-19 pneumonia. METHODS: This retrospective cohort study included 403 adult patients with moderate COVID-19 pneumonia who were admitted to Shenzhen Third People's Hospital, China. The antiviral drugs arbidol, interferon alpha-1b, lopinavir-ritonavir and ribavirin were distributed to the patients for treatment. The primary endpoint of this study was the time to develop severe illness. RESULTS: Of the 462 patients admitted, 403 had moderate COVID-19 symptoms at hospital admission and were included in this study. 90 of the 403 (22.3%) patients progressed to severe illness. The use of arbidol was associated with a lower severity rate 3.5% compared to control group 30.5%, p-value < 0.0001; the adjusted hazard ratio was 0.28 (95% CI: 0.084-0.90, p = 0.033). The use of interferon alpha-1b was associated with a lower severity rate 15.5% compared to control group 29.3%, with p-value < 0.0001; the adjusted hazard ratio was 0.30 (95% CI: 0.15-0.58, p =  0.0005). The use of lopinavir-itonavir and ribavirin did not show significant differences in adjusted regression models. Early use of arbidol within 7 days of symptom onset was significantly associated with a reduced recovery time of - 5.2 days (IQR - 3.0 to - 7.5, p = 4e-06) compared with the control group. CONCLUSION: Treatment with arbidol and interferon alpha-1b contributes to reducing the severity of illness in patients with moderate COVID-19 pneumonia. Early use of arbidol may reduce patients' recovery time.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , Indoles/administration & dosage , Interferon-alpha/administration & dosage , Adult , China , Drug Therapy, Combination , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Treatment Outcome
11.
World J Clin Cases ; 9(25): 7350-7357, 2021 Sep 06.
Article in English | MEDLINE | ID: covidwho-1456539

ABSTRACT

BACKGROUND: To date, no treatment has proven to be absolutely effective for coronavirus disease 2019 (COVID-19) patients, and further research is necessary. As a traditional antiviral drug, arbidol was widely used in Wuhan at the beginning of the COVID-19 epidemic and is of increasing interest for treating COVID-19 based on in vitro data suggesting activity against severe acute respiratory syndrome (SARS). Although arbidol has been widely used in China to treat COVID-19 patients, clinical trials to date have not clearly substantiated this approach. AIM: To evaluate the efficacy of arbidol for COVID-19. METHODS: A retrospective study was conducted on 132 moderate and severe COVID-19 patients admitted to Jinyintan Hospital and Huoshenshan Hospital (officially designated for COVID-19 treatment) from February to March 2020 in Wuhan, China. This study mainly evaluated the efficacy of arbidol in patients with COVID-19 in the early stage of the SARS coronavirus 2 epidemic. Arbidol was administered at a dose of 200 mg, three times a day, with a 10-d course to adults not receiving any other drugs. Due to the shortage of beds at the time, not every patient could be admitted immediately. We looked for the early stages of the sudden outbreak, places of limited medical resources, limited ward beds, and delayed admission; thus, some patients naturally fit into the control group who did not receive any antiviral drugs. Out of the 132 patients, 72 received arbidol treatment, and 60 did not. We compared the disease course of the two groups and explored the predictors of extended disease duration. RESULTS: Seventy-two patients commenced arbidol, and 60 patients did not receive arbidol treatment. The disease duration in the former group was shorter (23.42 ± 6.92 vs 29.60 ± 6.49, P < 0.001). Multivariate regression analysis showed that the risk of a prolonged course of disease increased by 7.158 times in the non-arbidol treatment group. Ferritin > 483.0 ng/mL and lactate dehydrogenase (LDH) > 237.5 U/L were found to be independent risk factors for protracted cases, with the risk of an extended disease duration increasing to 2.852 times and 5.946 times, respectively. CONCLUSION: The duration course of moderate and severe COVID-19 patients is reduced by 6.183 d when arbidol is administered. Ferritin > 486.5 ng/mL and LDH > 239.5 U/L are independent risk factors for delayed recovery from COVID-19. Early oral administration of arbidol 200 mg t.i.d. with a 10-d course of treatment may be an effective management strategy in COVID-19 patients, particularly those with increased serum ferritin or elevated LDH.

12.
Infect Prev Pract ; 2(3): 100061, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1450131

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which was declared a global pandemic by the World Health Organization on 11th March 2020. The treatment guidelines for COVID-19 vary between countries, yet there is no approved treatment to date. AIM: To report any evidence of therapeutics used for the management of patients with COVID-19 in clinical practice since emergence of the virus. METHODS: A systematic review protocol was developed based on the PRISMA statement. Articles for review were selected from Embase, Medline and Google Scholar. Readily accessible peer-reviewed, full articles in English published from 1st December 2019 to 26th March 2020 were included. The search terms included combinations of: COVID, SARS-COV-2, glucocorticoids, convalescent plasma, antiviral and antibacterial. There were no restrictions on the types of study eligible for inclusion. RESULTS: Four hundred and forty-nine articles were identified in the literature search; of these, 41 studies were included in this review. These were clinical trials (N=3), case reports (N=7), case series (N=10), and retrospective (N=11) and prospective (N=10) observational studies. Thirty-six studies were conducted in China (88%). Corticosteroid treatment was reported most frequently (N=25), followed by lopinavir (N=21) and oseltamivir (N=16). CONCLUSIONS: This is the first systematic review to date related to medication used to treat patients with COVID-19. Only 41 studies were eligible for inclusion, most of which were conducted in China. Corticosteroid treatment was reported most frequently in the literature.

13.
Front Pharmacol ; 12: 683296, 2021.
Article in English | MEDLINE | ID: covidwho-1430716

ABSTRACT

Background: In addition to supportive therapy, antiviral therapy is an effective treatment for coronavirus disease 2019 (COVID-19). Objective: To compare the efficacy and safety of favipiravir and umifenovir (Arbidol) to treat COVID-19 patients. Methods: We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Enrolled patients with initial symptoms within 12 days were randomly assigned in a 1:1 ratio to receive conventional therapy plus Arbidol (200 mg*3/day) or favipiravir (1600 mg*2/first day followed by 600 mg*2/day) for 7 days. The primary outcome was the clinical recovery rate at day 7 of drug administration (relief for pyrexia and cough, respiratory frequency ≤24 times/min; oxygen saturation ≥98%). Latency to relief for pyrexia and cough and the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV)/mechanical ventilation (MV) were the secondary outcomes. Safety data were collected for 17 days. Results: A total of 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive favipiravir (116 assessed), and 120 patients were assigned to receive Arbidol (120 assessed). The clinical recovery rate at day 7 of drug administration did not significantly differ between the favipiravir group (71/116) and Arbidol group (62/120) (p = 0.1396, difference in recovery rate: 0.0954; 95% CI: -0.0305∼0.2213). Favipiravir contributed to relief for both pyrexia (difference: 1.70 days, p < 0.0001) and cough (difference: 1.75 days, p < 0.0001). No difference was observed in the AOT or NMV/MV rate (both p > 0.05). The most frequently observed favipiravir-associated adverse event was increased serum uric acid (16/116, OR: 5.52, p = 0.0014). Conclusion: Among patients with COVID-19, favipiravir, compared to Arbidol, did not significantly improve the clinical recovery rate at day 7. Favipiravir significantly improved the latency to relieve pyrexia and cough. Adverse effects caused by favipiravir are mild and manageable.

14.
J Proteins Proteom ; 12(4): 257-270, 2021.
Article in English | MEDLINE | ID: covidwho-1427464

ABSTRACT

COVID-19 [coronavirus disease 2019] has resulted in over 204,644,849 confirmed cases and over 4,323,139 deaths throughout the world as of 12 August 2021, a total of 4,428,168,759 vaccine doses have been administered. The lack of potentially effective drugs against the virus is making the situation worse and dangerous. Numerous forces are working on finding an effective treatment against the virus but it is believed that a de novo drug would take several months even if huge financial support is provided. The only solution left with is drug repurposing that would not only provide effective therapy with the already used clinical drugs, but also save time and cost of the de novo drug discovery. The initiation of the COVID-19 infection starts with the attachment of spike glycoprotein of SARS-CoV-2 to the host receptor. Hence, the inhibition of the binding of the virus to the host membrane and the entry of the viral particle into the host cell are one of the main therapeutic targets. This paper not only summarizes the structure and the mechanism of spike protein, but the main focus is on the potential covalent spike protein inhibitors.

15.
Sci Total Environ ; 805: 150380, 2022 Jan 20.
Article in English | MEDLINE | ID: covidwho-1415774

ABSTRACT

An indole derivative umifenovir (Arbidol) is one of the most widely used antiviral drugs for the prevention and treatment of COVID-19 and some other viral infections. The purpose of the present study was to shed light on the transformation processes of umifenovir in municipal wastewater, including disinfection with active chlorine, as well as to assess the levels of the antiviral drug and its metabolites entering and accumulating in natural reservoirs under conditions of the SARS-CoV-2 pandemic. The combination of high-performance liquid chromatography with electrospray ionization high-resolution mass-spectrometry and inductively coupled plasma mass spectrometry was used for tentative identification and quantification of umifenovir and its transformation products in model reaction mixtures and real samples of wastewater, river water, biological sludge and bottom sediments taken at the wastewater treatment plant in Arkhangelsk, a large cultural and industrial center at the Russian North. Laboratory experiments allowed identifying fifteen bromine-containing transformation products, forming at the initial stages of the chlorination and fourteen classic volatile and semi volatile disinfection by-products with bromoform as the dominant one. Chlorinated derivatives are only the minor disinfection by-products forming by substitution of alkylamine group in the aromatic ring. The schemes of umifenovir transformation in reactions with dissolved oxygen and sodium hypochlorite are proposed. Two established primary transformation products formed by oxidation of the thioether group to sulfoxide and elimination of thiophenol were detected in noticeable concentrations in the wastewater together with their precursor. The level of umifenovir reached 1.3 mg kg-1 in the sludge and municipal wastewater treat contained 1 µg L-1 of that drug, while its removal during biological wastewater treatment was about 40%. Pronounced accumulation of umifenovir and its transformation products in biological sludge and bottom sediments of natural reservoirs may be a source of the future secondary pollution of the environment.


Subject(s)
COVID-19 , Water Pollutants, Chemical , Antiviral Agents , Humans , Indoles , Pandemics , SARS-CoV-2 , Waste Water , Water Pollutants, Chemical/analysis
16.
Curr Med Sci ; 41(6): 1096-1104, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1404664

ABSTRACT

OBJECTIVE: To study data about SARS-CoV-2 virus shedding and clarify the risk factors for prolonged virus shedding. METHODS: Data were retrospectively collected from adults hospitalized with laboratory-confirmed coronavirus disease-19 (COVID-19) in Wuhan Union Hospital. We compared clinical features among patients with prolonged (a positive SARS-CoV-2 RNA on day 23 after illness onset) and short virus shedding and evaluated risk factors associated with prolonged virus shedding by multivariate regression analysis. RESULTS: Among 238 patients, the median age was 55.5 years, 57.1% were female, 92.9% (221/238) were administered with arbidol, 58.4% (139/238) were given arbidol in combination with interferon. The median duration of SARS-CoV-2 virus shedding was 23 days (IQR, 17.8-30 days) with a longest one of 51 days. The patients with prolonged virus shedding had higher value of D-dimer (P=0.002), IL-6 (P<0.001), CRP (P=0.005) and more lobes lung lesion (P=0.014) on admission, as well as older age (P=0.017) and more patients with hypertension (P=0.044) than in those the virus shedding less than 23 days. Multivariate regression analysis revealed that prolonged viral shedding was significantly associated with initiation arbidol >8 days after symptom onset [OR: 2.447, 95% CI (1.351-4.431)], ≥3 days from onset of symptoms to first medical visitation [OR: 1.880, 95% CI (1.035-3.416)], illness onset before Jan. 31, 2020 [OR: 3.289, 95% CI (1.474-7.337)]. Arbidol in combination with interferon was also significantly associated with shorter virus shedding [OR: 0.363, 95% CI (0.191-0.690)]. CONCLUSION: Duration of SARS-CoV-2 virus shedding was long. Early initiation of arbidol and arbidol in combination with interferon as well as consulting doctor timely after illness onset were helpful for SARS-CoV-2 clearance.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , COVID-19/virology , Indoles/administration & dosage , SARS-CoV-2 , Virus Shedding , Adult , Aged , COVID-19/epidemiology , China/epidemiology , Cohort Studies , Female , Hospitalization , Humans , Interferons/administration & dosage , Logistic Models , Male , Middle Aged , Multivariate Analysis , Pandemics , RNA, Viral/analysis , Retrospective Studies , Risk Factors , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Time Factors , Virus Shedding/drug effects
17.
Immun Inflamm Dis ; 9(4): 1197-1208, 2021 12.
Article in English | MEDLINE | ID: covidwho-1340260

ABSTRACT

OBJECTIVE: To provide the latest evidence for the efficacy and safety of arbidol (umifenovir) in COVID-19 treatment. METHODS: A literature systematic search was carried out in PubMed, Cochrane Library, Embase, and medRxiv up to May 2021. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of included studies. Meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen studies were met the inclusion criteria. No significant difference was observed between arbidol and non-antiviral treatment groups neither for primary outcomes, including the negative rate of PCR (NR-PCR) on Day 7 (risk ratio [RR]: 0.94; 95% confidence interval (CI): 0.78-1.14) and Day 14 (RR: 1.10; 95% CI: 0.96-1.25), and PCR negative conversion time (PCR-NCT; mean difference [MD]: 0.74; 95% CI: -0.87 to 2.34), nor secondary outcomes (p > .05). However, arbidol was associated with higher adverse events (RR: 2.24; 95% CI: 1.06-4.73). Compared with lopinavir/ritonavir, arbidol showed better efficacy for primary outcomes (p < .05). Adding arbidol to lopinavir/ritonavir also led to better efficacy in terms of NR-PCR on Day 7 and PCR-NCT (p < .05). There was no significant difference between arbidol and chloroquine in primary outcomes (p > .05). No remarkable therapeutic effect was observed between arbidol and other agents (p > .05). CONCLUSION: The present meta-analysis showed no significant benefit of using arbidol compared with non-antiviral treatment or other therapeutic agents against COVID-19 disease. High-quality studies are needed to establish the efficacy and safety of arbidol for COVID-19.


Subject(s)
COVID-19 , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Indoles , SARS-CoV-2
18.
Pharmaceuticals (Basel) ; 14(8)2021 Jul 28.
Article in English | MEDLINE | ID: covidwho-1335170

ABSTRACT

Due to the lack of an etiologic treatment for SARS-CoV-2 and the difficulties involved in developing new drugs, some drugs already approved for other diseases or with efficacy against SARS and MERS, have been used in patients with COVID-19. This systematic review aims to summarize evidence on the efficacy and safety of five antivirals applied to patients with COVID-19, that have proven to be effective either in vitro studies or in studies on SARS-CoV and MERS.; An intensive search of different databases (Pub Med, WoS, MEDLINE and Cochrane COVID-19 Study Register) has been carried out until the end of April 2021. This systematic review has been conducted according to the PRISMA statement. From each of the included studies, the characteristics of the intervention and comparison groups, demographic data and results were extracted independently; Remdesivir is well tolerated and helps to accelerate clinical improvement but is ineffective in reducing mortality. Favipiravir is safe and shows promising results regarding symptom resolution but does not improve viral clearance. The use of lopinavir/ritonavir has been associated with an increased risk of gastrointestinal adverse events and it has not proven to be effective. No significant differences were observed between patients treated with ribavirin or umifenovir and their respective control groups; Remdesivir and favipiravir are well tolerated and effective in accelerating clinical improvement. This systematic review does not support the use of lopinavir/ritonavir, ribavirin and umifenovir in hospitalized patients with COVID-19.

19.
Pharmacol Res ; 157: 104859, 2020 07.
Article in English | MEDLINE | ID: covidwho-1318929

ABSTRACT

Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may limit spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Peptidyl-Dipeptidase A/drug effects , Pneumonia, Viral/drug therapy , Serine Endopeptidases/drug effects , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Humans , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , SARS-CoV-2 , Serine Proteinase Inhibitors/pharmacology
20.
Int Immunopharmacol ; 98: 107831, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1313172

ABSTRACT

Explicit hindrance and blockade of the viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is considered one of the most promising and efficient approaches for developing highly potent remedies for COVID-19. However, almost all of the reported viral RdRp inhibitors (either repurposed or new antiviral drugs) lack specific selectivity against the novel coronaviral RdRp and still at a beginning phase of advancement. Herein, I discovered and introduce a new pyrazine derivative, (E)-N-(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20), as the first potent SARS-CoV-2 RdRp inhibitor with very high selectivity (209- and 45-fold more potent than favipiravir and remdesivir, respectively). This promising selective specific anti-COVID-19 compound is also deemed to be the first distinctive derivative of favipiravir. Cyanorona-20, the unprecedented nucleoside/nucleotide analog, was designed, synthesized, characterized, computationally studied, and biologically evaluated for its anti-COVID-19 actions (through a precise in vitro anti-COVID-19 assay). The results of the biological assay displayed that cyanorona-20 surprisingly exhibited very high and largely significant anti-COVID-19 activities (anti-SARS-CoV-2 EC50 = 0.45 µM), and, in addition, it could be also a very promising guide and lead compound for the design and synthesis of new anti-SARS-CoV-2 and anti-COVID-19 agents through structural modifications and further computational studies. Further appraisal for the improvement of cyanorona-20 medication is a prerequisite requirement in the coming days. In a word, the ascent of the second member (cyanorona-20 "Corona Antidote") of the novel and promising class of anti-COVID-19 pyrazine derivatives would drastically make a medical uprising in the pharmacotherapeutic treatment regimens and protocols of the recently-emerged SARS-CoV-2 infection and its accompanying COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Enzyme Inhibitors/pharmacology , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/drug effects , Virus Replication/drug effects , Antiviral Agents/chemical synthesis , COVID-19/diagnosis , COVID-19/virology , Computer-Aided Design , Drug Design , Enzyme Inhibitors/chemical synthesis , Host-Pathogen Interactions , Humans , Molecular Docking Simulation , Molecular Structure , Molecular Targeted Therapy , RNA-Dependent RNA Polymerase/metabolism , SARS-CoV-2/enzymology , SARS-CoV-2/growth & development , Structure-Activity Relationship
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