https://www.pnas.org/content/early/2020/04/28/2007346117

Teams are pursuing a dizzying array of therapeutic strategies to stymie COVID-19. It’s not yet clear which approach, or combination of approaches, will work best.

In late February, when reports of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in California started to emerge, Nevan Krogan’s molecular biology lab went into overdrive. Everyone in the lab switched to studying how viral proteins affect host cells. The group, at the University of California, San Francisco, came up with a schedule of lab shifts to work around the clock while maintaining at least six feet of space between colleagues. Although a mass spectrometer broke down and the group failed to synthesize three viral proteins, the last pieces of data—revealing which host proteins interacted with viral proteins—came in just as the lab shut down to comply with the state’s shelter-in-place orders.

Last month, the team published a preprint describing 69 potential drugs—24 of them already approved by the US Food and Drug Administration (FDA) for other diseases—that could help treat coronavirus disease 2019 (COVID-19) patients. The team identified the drugs by studying how 26 of the virus’s 29 proteins interact with host cells (1). In cell cultures, the researchers used synthetic versions of viral proteins to uncover the human proteins that bound to each viral molecule. Then they identified small molecules that bind to the host proteins or otherwise interact with them via cellular pathways.

The host–virus interactions that Krogan’s lab identified offer up clues as to why this new coronavirus causes symptoms that range from diarrhea and an inability to smell, to pneumonia and fatal multiorgan failure. “Other coronaviruses are similar but not as virulent,” Krogan says. “In terms of protein interactions, this virus seems to hijack and rewire so many different cellular pathways—it gets its fingers into all the key machinery of a cell.”

 

https://www.ncbi.nlm.nih.gov/pubmed/32329881

2020 Apr;24(7):4040-4047. doi: 10.26355/eurrev_202004_20875.

Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience.

Abstract

OBJECTIVE:

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord.

PATIENTS AND METHODS:

This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV).

RESULTS:

We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days.

CONCLUSIONS:

Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.

PMID:
32329881
DOI:
10.26355/eurrev_202004_20875
[Indexed for MEDLINE]
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About COVID-therapy

May 2, 2020

https://doi.org/10.1016/j.jbspin.2020.03.011

Editorial

Urgent avenues in the treatment of COVID-19: Targeting downstream inflammation to prevent catastrophic syndrome

https://doi.org/10.1016/j.jbspin.2020.03.011

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