更新于：2024-11-01

Pan Coronavirus

泛冠状病毒

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与泛冠状病毒相关的药物

GEO-CM02

靶点

SARS-CoV-2 S protein

作用机制

SARS-CoV-2 S protein抑制剂

在研机构

GeoVax Labs, Inc.

原研机构

GeoVax Labs, Inc.

在研适应症

泛冠状病毒

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

TT-303

靶点-

作用机制-

在研机构

Tempo Therapeutics, Inc.初创企业

原研机构

Tempo Therapeutics, Inc.初创企业

在研适应症

泛冠状病毒

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

Pan-coronavirus inhibitor(Orthogon Therapeutics)

靶点-

作用机制-

在研机构

Orthogon Therapeutics LLC

原研机构

Orthogon Therapeutics LLC

在研适应症

泛冠状病毒

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与泛冠状病毒相关的临床结果

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100 项与泛冠状病毒相关的转化医学

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0 项与泛冠状病毒相关的专利（医药）

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项与泛冠状病毒相关的文献（医药）

2023-09-01·iScience

Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response

Article

作者: Xu, Lei ; Peppelenbosch, Maikel P ; Wang, Wenshi ; Li, Pengfei ; de Vries, Annemarie C ; Wang, Yining ; Crombag, Marie-Rose B S ; Pan, Qiuwei ; Kainov, Denis E ; Rottier, Robbert J

Severe infections with coronaviruses are often accompanied with hyperinflammation, requiring therapeutic strategies to simultaneously tackle the virus and inflammation. By screening a safe-in-human broad-spectrum antiviral agents library, we identified that indomethacin can inhibit pan-coronavirus infection in human cell and airway organoids models. Combining indomethacin with oral antiviral drugs authorized for treating COVID-19 results in synergistic anti-coronavirus activity. Coincidentally, screening a library of FDA-approved drugs identified indomethacin as the most potent potentiator of interferon response through increasing STAT1 phosphorylation. Combining indomethacin with interferon-alpha exerted synergistic antiviral effects against multiple coronaviruses. The anti-coronavirus activity of indomethacin is associated with activating interferon response. In a co-culture system of lung epithelial cells with macrophages, indomethacin inhibited both viral replication and inflammatory response. Collectively, indomethacin is a pan-coronavirus inhibitor that can simultaneously inhibit virus-triggered inflammatory response. The therapeutic potential of indomethacin can be further augmented by combining it with oral antiviral drugs or interferon-alpha.

2023-06-01·United European gastroenterology journal

Immunosuppressants exert differential effects on pan-coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir.

Article

作者: de Vries, Annemarie C ; Peppelenbosch, Maikel P ; Pan, Qiuwei ; Kamar, Nassim ; Li, Pengfei ; den Hoed, Caroline M ; Wang, Yining ; Lavrijsen, Marla ; Bruno, Marco J ; Rottier, Robbert J

BACKGROUNDImmunocompromised populations, such as organ transplant recipients and patients with inflammatory bowel disease (IBD) receiving immunosuppressive/immunomodulatory medications, may be more susceptible to coronavirus infections. However, little is known about how immunosuppressants affect coronavirus replication and their combinational effects with antiviral drugs.OBJECTIVEThis study aims to profile the effects of immunosuppressants and the combination of immunosuppressants with oral antiviral drugs molnupiravir and nirmatrelvir on pan-coronavirus infection in cell and human airway organoids (hAOs) culture models.METHODSDifferent coronaviruses (including wild type, delta and omicron variants of SARS-CoV-2, and NL63, 229E and OC43 seasonal coronaviruses) were used in lung cell lines and hAOs models. The effects of immunosuppressants were tested.RESULTSDexamethasone and 5-aminosalicylic acid moderately stimulated the replication of different coronaviruses. Mycophenolic acid (MPA), 6-thioguanine (6-TG), tofacitinib and filgotinib treatment dose-dependently inhibited viral replication of all tested coronaviruses in both cell lines and hAOs. The half maximum effective concentration (EC50) of tofacitinib against SARS-CoV-2 was 0.62 μM and the half maximum cytotoxic concentration (CC50) was above 30 μM, which resulted in a selective index (SI) of about 50. The anti-coronavirus effect of the JAK inhibitors tofacitinib and filgotinib is dependent on the inhibition of STAT3 phosphorylation. Combinations of MPA, 6-TG, tofacitinib, and filgotinib with the oral antiviral drugs molnupiravir or nirmatrelvir exerted an additive or synergistic antiviral activity.CONCLUSIONSDifferent immunosuppressants have distinct effects on coronavirus replication, with 6-TG, MPA, tofacitinib and filgotinib possessing pan-coronavirus antiviral activity. The combinations of MPA, 6-TG, tofacitinib and filgotinib with antiviral drugs exerted an additive or synergistic antiviral activity. Thus, these findings provide an important reference for optimal management of immunocompromised patients infected with coronaviruses.

2022-09-01·European Journal of Obstetrics & Gynecology and Reproductive Biology

Pregnancy and neonatal outcomes of COVID-19: The PAN-COVID study

Article

作者: Vrapi, Enxhi ; Amin, Allison ; Roland Berger, MD ; Mutema, E. ; Hassan, Wassim ; Halawa, Sherry ; Dixon, Caroline ; Roztočil, Aleš ; Flood, Chris ; Greer, Sandra ; Frankland, Lisa ; Rallis, Dimitrios ; Blunden, Susara ; Verma, Amit ; Hammond, Bev ; Kirby, N. ; RATHER, BA ; Woodward, Zoe ; Prefumo, Federico ; Sherris, Leanne ; Iliodromiti, Stamatina ; Bressington, Catherine ; Sobhy Bakry, Mohamed ; XIE, Mingxing ; Anim-Somuah, Millicent ; Liebling, Rachel ; Emmet, Louise ; Chester, Mark ; Martin, Hayley L. ; Panagiotis Christofidis, Plastiras ; Peers, Beth ; Kidwai, Salman ; Harris, Laura ; Mahdi, Amy ; Balling, Trevor ; Harrington, Siân C ; Bale, Nichola ; Darmawan, Ernawati ; Milton, R. ; Townson, J. ; Playle, R. ; Jones, Sharon ; Glenn-Sansum, Coralie ; Perkins, Donna ; Newport, Rachel ; Hughes, Robin ; Chapman, Lianne ; Javaid, Muglu ; Wixted, Donna ; Crawford, Isobel ; Meadows, Emma ; Coxon, Sarah ; Higgins, Shelly ; Khare, Manjiri ; Vasu, Vimal ; Hinshaw, Kim ; Davies, Ru ; Tiziana Frusca, SSA ; Jennings, Jacqui ; Margarit, Lavinia ; Cantliffe, Jane ; Murtha, Victoria ; Bishop, Linda ; Raven, Jamie-Louise ; Bray, Maryanne ; Millward, Helen ; Cloherty, Karen ; Giri, Vibha ; Brain, Jessie ; Owen, Hilary ; Shah, Ahmar ; Nallapeta, Soum ; Chiu Yee POON, Liona ; Parra-Cordero, Mauro ; O'Brien, Clare ; Jokhi, Roobin ; Lee, Fidelma ; Churchill, David ; Atkinson, Vicki ; Tipper, Jacqueline ; Wee, Ling ; Robinson, Sophie ; Romero, Elena ; Jaleel, Shazia ; Grozeva, D. ; Watkins, Karen ; Mead, Joanna ; Rand, Abby ; MK Jarvie, Eleanor ; Windsor, Laurie ; Möller-Christensen, Christine ; Black, Mairead ; Mason, Nicky ; Harrington, Andrea ; Knight, Caroline ; Andrasova, Martina ; Syson, Jennifer ; Gerede, Angeliki ; Armstrong, Maggie ; Barker, Katie ; Gbinigie, Helen ; Elliott, Kerry ; Aladangady, Narendra ; Grigsby, Stephanie ; Huson, Coralie ; Everden, Caroline ; Glyn-Jones, Liz ; Grindey, Julie ; Wu, Pensée ; Malarselvi, Mani ; Wyatt, Cheryl ; Zill-e-Huma, Rabia ; Barra, Fabio ; McKeown, Gillian ; Sukrutha, Veerareddy ; Khunda, Aethele ; Arya, Rita ; Anderson, Michelle ; Mansfield, Roshni ; Sinha, Barkha ; Stables, Sarah ; Dall'Asta, Andrea ; Revell, Kirsty ; Sameena Kausar, Ms ; Cresswell, Janet ; Kermack, Alexandra J ; Goddard, Julie ; Gorti, Mahalakshmi ; Banerjee, J. ; Mullins, E. ; Camarasa, Laura ; Asghar, Anila ; Essien, Sandra ; McCooty, Shanteela ; Ahmed, Amna ; Divakar, Hema ; Shah, Neil ; Ekladios, Sarah ; Perry, A. ; Ajay, Bini ; Germán Caro, Waldo ; Heal, Carrie ; Aldika Akbar, M.I ; Davies, Ruth ; Gowans, Sharon ; Lees, C. ; Kousar, Rukhsana ; Mills, Emma ; Gada, Ruta ; Southam, Donna ; Elbahnasawy, Mohamed ; Satodia, Prakash ; Nejad, Avideah ; Tanton, Emma ; Fayadh, Anam ; Mackay, Ami ; Swaminathan, Louise ; Bourne, T. ; Ratcliffe, Sam ; Robinson, Kate ; Nicoll, Antony ; Bourke, Miriam ; Collins, Emma ; Narayanan, Sankara ; Viner, Alexandra ; Rajeswary, Ms.Jyothi ; Mossop, Jude ; Radford, Jane ; Garner, Zoe

OBJECTIVETo assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection.METHODSProspective, web-based registry. Pregnant women were invited to participate if they had suspected or confirmed SARS-CoV-2 infection between 1st January 2020 and 31st March 2021 to assess the impact of infection on maternal and perinatal outcomes including miscarriage, stillbirth, fetal growth restriction, pre-term birth and transmission to the infant.RESULTSBetween April 2020 and March 2021, the study recruited 8239 participants who had suspected or confirmed SARs-CoV-2 infection episodes in pregnancy between January 2020 and March 2021. Maternal death affected 14/8197 (0.2%) participants, 176/8187 (2.2%) of participants required ventilatory support. Pre-eclampsia affected 389/8189 (4.8%) participants, eclampsia was reported in 40/ 8024 (0.5%) of all participants. Stillbirth affected 35/8187 (0.4 %) participants. In participants delivering within 2 weeks of delivery 21/2686 (0.8 %) were affected by stillbirth compared with 8/4596 (0.2 %) delivering ≥ 2 weeks after infection (95 % CI 0.3-1.0). SGA affected 744/7696 (9.3 %) of livebirths, FGR affected 360/8175 (4.4 %) of all pregnancies. Pre-term birth occurred in 922/8066 (11.5%), the majority of these were indicated pre-term births, 220/7987 (2.8%) participants experienced spontaneous pre-term births. Early neonatal deaths affected 11/8050 livebirths. Of all neonates, 80/7993 (1.0%) tested positive for SARS-CoV-2.CONCLUSIONSInfection was associated with indicated pre-term birth, most commonly for fetal compromise. The overall proportions of women affected by SGA and FGR were not higher than expected, however there was the proportion affected by stillbirth in participants delivering within 2 weeks of infection was significantly higher than those delivering ≥ 2 weeks after infection. We suggest that clinicians' threshold for delivery should be low if there are concerns with fetal movements or fetal heart rate monitoring in the time around infection. The proportion affected by pre-eclampsia amongst participants was not higher than would be expected, although we report a higher than expected proportion affected by eclampsia. There appears to be no effect on birthweight or congenital malformations in women affected by SARS-CoV-2 infection in pregnancy and neonatal infection is uncommon. This study reflects a population with a range of infection severity for SARS-COV-2 in pregnancy, generalisable to whole obstetric populations.