Scientists at Sanford Burnham Prebys Medical Discovery Institute, the University of Hong Kong, Scripps Research, UC San Diego School of Medicine, the Icahn School of Medicine at Mount Sinai and UCLA have identified 30 existing drugs that stop the replication of SARS-CoV-2, the virus that causes Covid-19. Almost all of the drugs are entirely different from those currently being tested in clinical trials, and weren’t previously known to hold promise for Covid-19 treatment. The new candidates expand the number of “shots on goal” for a potential Covid-19 treatment and could reach patients faster than drugs that are created from scratch. The study was placed on bioRxiv – https://www.biorxiv.org/content/10.1101/2020.04.16.044016v1 – an open-access distribution service for preprints of life science research.
“We believe this is one of the first comprehensive drug screens using the live SARS-CoV-2 virus, and our hope is that one or more of these drugs will save lives while we wait for a vaccine for Covid-19,” said Sumit Chanda, Ph.D., director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys and senior author of the study. “Many drugs identified in this study – most of which are new to the Covid-19 research community – can begin clinical trials immediately or in a few months after additional testing.”
The drugs were identified by screening more than 12,000 drugs from the ReFRAME drug repurposing collection – a library of existing drugs that have been approved by the FDA for other diseases or have been tested extensively for human safety. ReFRAME was created by Scripps Research with support from the Bill & Melinda Gates Foundation to accelerate efforts to fight deadly diseases. Every compound was tested against the live SARS-CoV-2 virus, isolated from patients in Washington State and China, and the final 30 drugs were selected based on their ability to stop the virus’s growth.
“For us, the starting point for finding any new antiviral drug is to measure its ability to block viral replication in the lab,” says Chanda. “Since the drugs we identified in this study have already been tested in humans and proven safe, we can leapfrog over the more than half decade of studies normally required to get approval for human use.”
Highlights of the scientists’ discoveries follow. Each drug or experimental compound requires further evaluation in clinical trials to prove its effectiveness in treating people with Covid-19 before it can be used broadly.

• 27 drugs that are not currently under evaluation for Covid-19 were effective at halting viral replication. 17 of these drugs have an extensive record of human safety from clinical studies in non-Covid-19 diseases, including four—clofazimine, acitretin, tretinoin and astemizole—that were previously approved by the FDA for other indications.
• Thus far, six of the 17 were shown to be effective at concentrations, or doses, likely to be effective and tolerable in humans. Four of these six drugs – apilimod, MLN-3897, VBY-828 and ONO 5334 – have been tested clinically for diseases including rheumatoid arthritis, Crohn’s disease, osteoporosis and cancer.
• In addition to the 27 drug candidates, three drugs currently in clinical trials for Covid-19, including remdesivir and chloroquine derivatives, were also shown to be effective at stopping the growth of SARS-CoV-2. These results reaffirm their promise as potential Covid-19 treatments and support the continuation of ongoing clinical trials to prove their effectiveness in patients.
• Depending on regulatory guidance, the newly identified drug candidates may proceed directly to Covid-19 clinical trials or undergo further testing for efficacy in animal models.

“Based on the extensive data in this study, we believe the four drugs described above—apilimod, MLN-3897, VBY-825 and ONO 5334 – represent the best new approaches for a near-term Covid-19 treatment,” says Chanda. “However, we believe that all 30 drug candidates should be fully explored, as they were clearly active and effective at halting viral replication in our tests.”
“We have chosen to release these findings to the scientific and medical community now to help address the current global health emergency,” Chanda continues. “The data from this drug screen is a treasure trove; and we will continue to mine the data from this analysis, with a goal to find additional candidate therapies – and combinations of drugs – as they are identified.”

Researchers from the Department of Experimental Psychology at the University of Oxford have developed a new mental health treatment programme to provide frontline healthcare workers with one-to-one support, including fast-track access to post-traumatic stress disorder (PTSD) or depression treatment. This evidence-based programme, called SHAPE Recovery < www.shaperecovery.com >, builds on an outreach programme shown to reduce rates of PTSD and depression.
SHAPE Recovery is working with 3,300 frontline healthcare workers across England and has now been invited to work with 8,000 London Ambulance employees and staff from associated partner organisations.
Around the world, frontline healthcare workers, such as intensive care doctors, nurses, support staff and paramedics, are risking their lives daily to stem the tide of the COVID-19 pandemic. They are at an increased risk of developing mental health problems, such as PTSD as well as depression, sleep problems and anxiety. Although many hospitals offer well-being initiatives, there is little evidence to support their effectiveness and they require staff to come forward for help.
Associate Professor Jennifer Wild, Programme Lead, said: “SHAPE is based on 15 years of research to examine what predicts PTSD and depression in frontline workers. We used the findings from these studies to create a highly effective support programme to prevent the development of PTSD and depression. SHAPE is the outcome of this work. It is evidence-based, affordable, and with ongoing evaluation could, if needed, be incorporated within NHS services within 12 to 24 months. The aim is to support staff to stay well, to recover if unwell, and to continue to be able to work, providing much-valued patient care.”
Zidan Mozumder, a paramedic who has benefitted from the progamme, commented: “Work-related stress has been at an all-time high for my peers due to the current COVID-19 pandemic. Fortunately, though, my weekly calls with my well-being coach have mitigated that stress significantly. For this I am eternally grateful. I feel very lucky to have had all of this support.”
SHAPE is unique because it moves the burden of outreach for help from frontline staff to well-being coaches. This means staff don’t have to come forward for help. Instead, they can access one-to-one confidential help, independent from their employers, on their phones. In addition, SHAPE facilitates fast access to gold-standard treatment for PTSD and depression should it be indicated.
Data collected from the programme will help Oxford researchers determine:

• the effectiveness of this evidence-based, well-being support compared with no support for reducing symptoms of PTSD, depression, anxiety and sleep problems of frontline staff
• whether early intervention for staff who continue to work during the pandemic leads to their recovery from mental ill health
• potential cost savings of the programme to the NHS and society

Chinese researchers have for the first time shown in a pilot study that the use of convalescent plasma from cured COVID-19 patients provides promising results in the treatment of others with more severe disease.
In the preprint study at medRxiv (http://doi.org/dqrs; 2020), K. Duan et al. report that the administration of a single, high-dose of neutralizing antibodies is safe and provides encouraging results with regards to the reduction of viral load and improvement of clinical outcomes.
In the study, ten severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents.
After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). All patients showed significant improvement in or complete disappearance of clinical symptoms – including fever, cough, shortness of breath, and chest pain – within 3 days.
The authors state that along with increased oxyhaemoglobin saturation – indicative of recuperating lung function – several parameters also improved, including increased lymphocyte counts and decreased C-reactive protein. Radiological examinations showed varying degrees of absorption of lung lesions within 7 days. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed.
The study shows that CP therapy could potentially improve clinical outcomes through neutralizing viremia in severe COVID-19 cases, however, the authors note that further investigation is needed in larger well-controlled trials to assess the optimal dose and time point.

As the COVID-19 pandemic upends life as people know it, changing daily routines, limiting social interactions and shaking their sense of safety, a mental health experts from U.S. hospital Cleveland Clinic’s Mellen Center is stressing that it is perfectly acceptable to feel sad about all of it.
She points out that grief is a natural response to loss – whether it is the loss of a loved one, or the loss of a sense of normalcy.
“We are experiencing a lot of disappointment right now – in both small and big ways – and grief is going to be a factor,” says clinical health psychologist Amy Sullivan, PsyD, ABPP.
“It’s really important that we process this and stay connected to other people in safe ways,” she adds.
Regarding how people should go about dealing with all of these difficult and unexpected feelings bubbling up, she says there is no right or wrong way. However, she offers four suggestions that can help people to cope with current events.
1. Look through the lens of grief and process emotions
She says that the stages of grief can provide a helpful framework for navigating these complex emotions. Experts recognize these stages as denial, anger, bargaining, despair, and acceptance. However, these experts also know that people do not step neatly from one stage to the next in this exact order, she says.
“Grief can come in waves and change on a very regular basis. Our feelings can change on a daily, or even an hourly, basis,” she explains.
Dr. Sullivan adds it is normal to go from feeling despair one day to anger the next.
“The first thing we need to do is to recognize that it is normal to have these waves of emotions that are happening on a regular basis,” Dr. Sullivan says.
Next, she says, acknowledge the loss whether it is knowing or losing someone with COVID-19, losing jobs, missing friends or family.
“Those are all very sad, difficult things for people to manage,” Dr. Sullivan says.
“Feel what you are feeling – whether it is being overwhelmed, anxious, powerless or anything else, it can help to identify and name these emotions,” she advises.
“It can be quite powerful to sit with those feelings for a few moments – to really recognize those emotions and normalize them,” she says.
However, she advises people to set a time limit on this, suggesting they give themselves five minutes to feel that emotion, and then move on to something that they know is a positive coping skill for them.
“It is important for us to accept where our feelings are at the moment and process through them, and then move into a more positive position of acceptance,” she says.
She says this can be done by identifying their own best coping mechanisms
“This is a time when people need to become innovative and develop their own individual sense of coping that works for them during this time,” she says. Examples might include deep breathing, mindfulness exercises, journaling, talking with another person, or going for a walk.
“If it comes to a point where someone cannot handle these feelings on their own, they need to seek mental health help,” Dr. Sullivan says.
2. Fight the urge to disengage
Dr. Sullivan stresses that staying connected is a powerful tool for coping during hard times. Whether that comes in the form of video chatting or sending a good old-fashioned letter, staying in touch with family, friends, neighbours and coworkers can help people to keep a positive attitude, she says.
She adds that many trained mental and behavioural health professionals are currently seeing patients through virtual visits, so that if people are having trouble coping, this could be a solution.
3. Focus on what can be controlled
Dr. Sullivan says that when there is so much uncertainty about the future, it is easy for people to get carried away, playing out the worst-case scenarios in their heads, for example worrying about themselves or someone else getting COVID-19, or wondering if things will ever get back to normal.
“Anticipating negative events can bring a sense of anxiety or fear,” Dr. Sullivan says.
She advises that, instead of agonizing over the things that cannot be known or controlled, people should be aware of what they do have control over. For example, they can choose how much news or social media they consume in a day, and they can decide what they eat. She recommends being mindful about these choices, and focusing on staying in the present.
4. Be open to joy
Lastly, Dr. Sullivan advises people to find joy and gratitude in the small things, like a video chat with family members, or the rush of fresh air when they open a window or step outside. She adds that if they are under a lockdown order, they can find ways to appreciate the opportunity to step back from the hustle and bustle of everyday life and being home.