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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329660

ABSTRACT

Following Delta, Omicron variant triggered a new wave of SARS-CoV-2 infection globally, adaptive evolution of the virus may not stop, the development of broad-spectrum antivirals is still urgent. We previously developed two hetero-bivalent nanobodies with potent neutralization against original WT SARS-CoV-2, termed aRBD-2-5 and aRBD-2-7, by fusing aRBD-2 with aRBD-5 or aRBD-7, respectively. Here, we resolved crystal structures of these nanobodies in complex with RBD, and found the epitope of aRBD-2 differs from that of aRBD-5, aRBD-7. aRBD-2 binds to a conserved epitope which renders its binding activity to all variants of concern (VOCs) including Omicron. Interestingly, although monovalent aRBD-5 and aRBD-7 lost binding to some variants, they effectively improved the overall affinity when transformed into the hetero-bivalent form after being fused with aRBD-2. Consistent with the high binding affinities, aRBD-2-5-Fc and aRBD-2-7-Fc exhibited ultra-potent neutralization to all five VOCs;particularly, aRBD-2-5-Fc neutralized authentic virus of Beta, Delta and Omicron with the IC50 of 5.98~9.65 ng/mL or 54.3~87.6 pM. Importantly, aRBD-2-5-Fc provided in vivo prophylactic protection for mice against WT and mouse-adapted SARS-CoV-2, and provided full protection against Omicron in hamster model when administrated either prophylactically or therapeutically. Taken together, we found a conserved epitope on RBD, and hetero-bivalent nanobodies had increased affinity for VOCs over its monovalent form, and provided potent and broad-spectrum protection both in vitro and in vivo against all tested major variants, and potentially future emerging variants. Our strategy provides a new solution in the development of therapeutic antibodies for COVID-19 caused by newly emergent VOCs.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329417

ABSTRACT

SARS-CoV-2 has infected more than 400 million people around the globe and caused millions of deaths. Since its identification in November 2021, Omicron, a highly transmissible variant, has become the dominant variant in most countries. Omicron highly mutated spike protein, the main target of vaccine development, significantly compromises the immune protection from current vaccination. We develop an mRNA vaccine (SOmicron-6P) based on an Omicron-specific sequence. In mice, SOmicron-6P shows superior neutralizing antibodies inducing abilities to a clinically approved inactivated virus vaccine, a clinically approved protein subunit vaccine, and an mRNA vaccine (SWT-2P) with the same sequence of BNT162b2 RNA. Significantly, SOmicron-6P induces a 14.4~27.7-fold and a 28.3~50.3-fold increase of neutralizing activity against the pseudovirus of Omicron and authentic Omicron compared to SWT-2P, respectively. In addition, two doses SOmicron-6P significantly protects Syrian hamsters against challenge with SARS-CoV-2 Omicron variant and elicits high titers of nAbs in a dose-dependent manner in macaques. Our results suggest that SOmicron-6P offers advantages over current vaccines, and it will be helpful for those with weak immunity.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325222

ABSTRACT

BACKGROUND: Previous study suggested that Chinese Herbal Medicine (CHM) Formula Huashibaidu granule might shorten disease course of Corona Virus Disease 2019 (COVID-19) patients. Our research aims to investigate the early treatment effect of Huashibaidu granule in mild COVID-19 patients under well clinical management.METHODS: An unblended cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. 2 cabins were randomly allocated to CHM or control group, with 204 randomly sampled mild COVID-19 patients in each cabin. All participants received a 7-day conventional treatment, and CHM group cabin used additional Huashibaidu granule 10g twice daily. Participants were followed up until they met clinical endpoint. The primary outcome was patient become worsening before clinical endpoint occurred. The secondary outcomes was discharge with cure before clinical endpoint occurred and relief of composite symptoms after 7 days treatment.FINDINGS: All 408 participants were followed up to meet clinical endpoint and included in statistical analysis. The baseline characteristics were comparable between 2 groups. The number of worsening patients in the CHM group was 5 (2.5%), and that in the control group was 16 (7.8%). There was a significant difference between groups (P=0.014). 8 foreseeable mild adverse events occurred without statistical difference between groups.INTERPRETATION: 7-day early treatment with Huashibaidu granule reduced worsening conversion of mild COVID-19 patients. Our study supports Huashibaidu Granule as an active option for early treatment of mild COVID-19 in similar medical locations with well management.TRIAL REGISTRATION: The Chinese Clinical Trial Registry: ChiCTR2000029763.FUNDING: This study was supported by “National Key R&D Program of China” (No.2020YFC0841500).DECLARATION OF INTERESTS: The authors guaranteed that there existed no competing interest in this paper.ETHICS APPROVAL STATEMENT: Ethics Review Committee of Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences Approval of Ethical Review Acceptance Number: S2020-001;Approval Number: P20001/PJ01.

4.
Front Med (Lausanne) ; 8: 696976, 2021.
Article in English | MEDLINE | ID: covidwho-1450816

ABSTRACT

Background: Previous research suggested that Chinese Medicine (CM) Formula Huashibaidu granule might shorten the disease course in coronavirus disease 2019 (COVID-19) patients. This research aimed to investigate the early treatment effect of Huashibaidu granule in well-managed patients with mild COVID-19. Methods: An unblinded cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. Two cabins were randomly allocated to a CM or control group, with 204 mild COVID-19 participants in each cabin. All participants received conventional treatment over a 7 day period, while the ones in CM group were additionally given Huashibaidu granule 10 g twice daily. Participants were followed up to their clinical endpoint. The primary outcome was worsening symptoms before the clinical endpoint. The secondary outcomes were cure and discharge before the clinical endpoint and alleviation of composite symptoms after the 7 days of treatment. Results: All 408 participants were followed up to their clinical endpoint and included in statistical analysis. Baseline characteristics were comparable between the two groups (P > 0.05). The number of worsening patients in the CM group was 5 (2.5%), and that in the control group was 16 (7.8%) with a significant difference between groups (P = 0.014). Eight foreseeable mild adverse events occurred without statistical difference between groups (P = 0.151). Conclusion: Seven days of early treatment with Huashibaidu granule reduced the likelihood of worsening symptoms in patients with mild COVID-19. Our study supports Huashibaidu granule as an active option for early treatment of mild COVID-19 in similar well-managed medical environments. Clinical Trial Registration:www.chictr.org.cn/showproj.aspx?proj=49408, identifier: ChiCTR2000029763.

5.
Front Med (Lausanne) ; 7: 373, 2020.
Article in English | MEDLINE | ID: covidwho-689146

ABSTRACT

Background: With the adoption of powerful preventive and therapeutic measures, a large number of patients with COVID-19 have recovered and been discharged from hospitals in Wuhan, China. Prevention of epidemic rebound is a top priority of current works. However, information regarding post-discharge quarantine and surveillance of recovered patients with COVID-19 is scarce. Methods: This study followed up 337 patients with COVID-19 in a Wuhan East-West Lake Fangcang shelter hospital during the post-discharge quarantine. Demographic, clinical characteristics, comorbidities, and chest computed tomography (CT) image, mental state, medication status, and nucleic acid test data were summarized and analyzed. Results: 21/337 (6.2%) patients were SARS-CoV-2 nucleic acid re-positive, and 4 /337(1.2%) patients were suspected positive. The median day interval between the discharge to nucleic acid re-positivity was 7.5 days (IQR, 6-13), ranging from 6 to 13 days. Cough/expectoration are the most common symptoms, followed by chest congestion/dyspnea during the 2 weeks post-discharge quarantine. Risk factors of nucleic acid re-positivity including the number of lobes infiltration (odds ratio[OR], 1.14; 95% CI, 1.09-1.19), distribution (OR, 0.16; 95% CI, 0.13-0.19), CT imaging feature of patchy shadowing accompanying with consolidation (OR, 9.36; 95% CI, 7.84-11.17), respiratory symptoms of cough accompanying with expectoration (OR, 1.39; 95% CI, 1.28-1.52), and chest congestion accompanying by dyspnea (OR, 1.42; 95% CI, 1.28-1.57). Conclusion: The 2 weeks post-discharge quarantine may be an effective measure to prevent the outbreak from rebounding from the recovered patients. The second week is a critical period during post-discharge quarantine. Special attention should be paid to cough, expectoration, chest congestion, and dyspnea in recovered COVID-19 patients. A few recovered patients may prolong the quarantine based on clinical symptoms and signs and nucleic acid results in the 2 weeks of medical observation.

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