COVID-19 – Interprofessional Health Sciences Library

Preparing Drugs Ahead of Viral Disease Outbreak

Last month’s announcement^[1] from the National Institute of Allergy and Infectious Disease that it was funding 9 research consortia – called “Antiviral Drug Discovery Centers for Pathogens of Pandemic Concern”, was welcome news. The idea that a concerted effort will be made to create COVID-19 antivirals, as well as ones targeting a range of (viral) families in anticipation of the next outbreak, is inspired. Bringing together academic researchers with pharmaceutical/industrial partners focused on multidisciplinary approaches is a real strength of the envisioned program. Congratulations to Dr. David Perlin (from the Hackensack Meridian Health Research Institute’s Center for Discovery and Innovation) and his collaborators for being selected as part of the program’s drug development initiative.^[2]

Complementing the power of antivirals and their ability to alter the course of disease and/or reduce and prevent viral spread, are vaccines – designed to prevent infection altogether. The following discussion focuses on steps to accelerate development of just such antiviral vaccines.

Let us be clear – viruses have long been, and will continue to be, a plague on human health and well-being. Whether they be extant (e.g., SARS-CoV2, Ebola, West Nile), newly mutated variants, or recently developed from zoonotic (i.e., animal to human) transmission – infectious viruses will continue to do what they have done for thousands of years – copy and spread their genomes and compromise human health. How do we get out in front of this incoming and indeed ever-present onslaught? The answer is to prepare now.

Dr. Florian Krammer at the Icahn School of Medicine at Mount Sinai suggests that some 50-100 viruses should be identified and targeted for vaccine development.^[3] Choice of which viruses to pursue would be based on infective potential, transmissibility, and accompanying symptoms/pathology. Such a curated list of potentially dangerous pathogens could be informed by recently developed approaches involving machine learning/artificial intelligence. Georgetown University researcher Dr. Colin Carlson and team have been working on just such approaches and have launched VIRION, a database (still in alpha testing) that is designed to help with the curation process. Powerful algorithms coupled with predictive modeling and detailed analytics allow, for the first time, an ability to predictably identify viruses with enhanced potential to infect humans.

Vaccine development in response to the COVID-19 pandemic proceeded at a pace unseen in modern medicine. Vaccine platforms are now in place such that even tighter timelines between virus identification and vaccine production may be realized. But every day – especially early in an outbreak – is critical and could mean the difference between life and death; so how can the program be maximally accelerated? Perhaps, as Dr. Krammer suggests, once viruses (and viral families) are identified, the process of vaccine development could commence. Not waiting for an actual viral outbreak across human populations is crucial.

mRNA-based vaccine development, which worked so well in the context of SARS-CoV2, could once again be brought to bear. Moderna’s mRNA Access program^[4] would be particularly helpful here – assisting in the identification of appropriate antigen(s), the design of relevant mRNA coding sequences, and other stability, expression, and production parameters associated with its (mRNA) vaccine platform. Once candidate vaccines were developed and tested pre-clinically, they could be evaluated in FDA-approved phase 1 and 2 (drug) testing protocols. Having the results of such clinical trials would position the vaccines for rapid deployment in phase 3 testing when circumstances warranted. Once it is clear a (related) virus has been identified and an outbreak is imminent, scaled up production, distribution, and inoculation efforts would be rapidly initiated. What might have taken years in the past and took roughly a year for the COVID-19 vaccine, could now be accelerated to, Dr. Krammer predicts, 3-4 months (after identification of the relevant viral strain). The value of such preparedness in terms of reducing and/or eliminating the disease burden is incalculable. There are many hurdles (e.g., regulatory, monetary, coordination) that would need to be overcome to effect such a strategy – but the impact could truly be life-saving on a world-wide scale.

SRT – June 2022

[1] https://www.nih.gov/news-events/news-releases/nih-announces-antiviral-drug-development-awards
[2] https://njbiz.com/65m-grant-funds-joint-academic-pharma-drug-accelerator/
[3] Krammer, F. (2020). Pandemic vaccines: how are we going to be better prepared next time? Med, 1(1), 28-32.
[4] https://mrna-access.modernatx.com

Weekend Hours Start April 24

Starting Saturday, April 24th the IHS Campus, including the IHS Library, will be open to students, faculty, and staff on weekends from 8:00am to 4:00pm.

Students are encouraged to utilize the library and student lounges only. No classroom doors will be opened for students unless authorized by a present faculty or staff member.

Please be advised, all parking procedures will be strictly enforced. Students must have a valid parking permit to be granted access into the South Lot.

All standard campus COVID-19 precautions will remain in place. Please continue to maintain proper social distancing and wear a mask.

mRNA Technology: A Shot in the Arm for Development of New Drug Therapies

As millions the world over receive mRNA-based vaccinations for COVID-19, there is hope that the virus and its attendant wanton destruction may soon be in our collective rear view mirrors. Other vaccine approaches, for example employing viral vectors, are making their way into the armamentarium of anti COVID-19 treatment options – the news just keeps getting better. The focus here is on mRNA technology – how did we get to this point, and what does it mean for the future?

mRNA vaccine COVID — Image Source: MIT News

The central dogma of molecular biology – loosely defined – states that DNA instructs mRNA creation, which directs protein synthesis. Ultimately, of course, it is the protein or enzyme created that is the molecule missing or defective in disease or needed to create immunity. DNA/gene-based therapies have existed for some time and recent advances have begun to overcome early technical problems encountered. The use of protein biologics – molecules produced in living cell “factories,” have also emerged as a viable option to treat protein/enzyme deficiencies or to introduce specifically designed functional antibodies. However, as a protein biochemist who has developed protocols for purifying enzymatically active protein biologics, I can assure you the process is exquisitely complex, time consuming, and costly. The approach can and has worked – it is simply a matter of committing the time and resources to empirically determining/optimizing the purification protocols.

Another option has emerged – specifically, the development of mRNA technologies as a mechanism to induce protein/enzyme expression. Again, as pointed out above – it is not that the role of mRNA in protein synthesis was unclear, rather, there were technical problems attendant to the approach. Let’s consider some of these previous limitations and how they were overcome to allow mRNA to be an efficient messenger of protein synthesis in humans.

mRNA is exquisitely unstable. RNAases – enzymes which break down mRNAs, are very efficient and ever present. mRNA will not enter cells, and if they could be transported, their mere presence often elicits an immune response. Couple this with relatively low protein yields from the cell’s translation processes – and the need for repeated dosing is manifest. So, what has changed?

First, Karikó and coauthors showed that employing specifically modified nucleosides in the design and synthesis of an mRNA molecule would render it far less immunogenic.¹ A great first step! Next, the sequence of the mRNA coding region (the area that encodes the information for the protein itself) would take advantage of what was known about (protein) translation. That is, some codons (~mRNA sequences that encode specific amino acids) are expressed more efficiently than others – resulting in greater overall protein yields. Recall that most amino acids are encoded by more than one codon, that is, the genetic code is degenerate. Detailed structural analyses of mRNAs also yielded new information about the importance of 5’ and 3’ untranslated regions in terms of the molecule’s overall stability and translational efficiency. A more complete understanding of mRNAs’ 5’ cap and 3’ poly (A) tail served to further extend the ability to preserve the molecule’s integrity.

Next, it was necessary to design a delivery system – a mechanism that would both protect the mRNA molecule, as well as assure its entry into cells. Many approaches were tested – lipid nanoparticles emerged as an efficient option. Once encapsulated and introduced into tissues, the mRNAs are internalized into cells by endocytosis – basically an engulfment of the lipid vesicle by the cell’s plasma membrane. Once inside the cell – the nascent endosome degranulates and the mRNA molecule is able to emerge into the cytoplasm and begin directing protein synthesis. The cell itself thus makes the protein.

Where does the technology go from here? The answer – quite simply, is that mRNA therapy could potentially be a suitable approach to treat many human diseases. Single enzyme deficiencies constitute a large class of lysosomal storage diseases (e.g., Tay-Sachs or Inclusion-cell (I-cell)), inherited metabolic diseases (e.g., Gaucher or Hunter syndrome), and peroxisomal diseases (e.g., acyl-CoA oxidase or D-bifunctional protein deficiency). Arginase deficiency and cystic fibrosis (caused by the dysfunctional cystic fibrosis transmembrane conductance regulator molecule) are two additional proteins whose missing or defective activities are associated with disease and whose replacement is being sought through mRNA therapies. Designing and synthesizing appropriate mRNAs is relatively straightforward, as is lipid nanoparticle encapsulation. Cold chain handling of the resultant therapeutic remains a requirement – but what a small price to pay for what could be life-changing medicines. It would not be inappropriate to say “the sky is the limit” with respect to the potential of mRNA-based protein/enzyme replacement therapeutics.

SRT – February 2021

Reference:

[1] K. Karikó, M. Buckstein, H. Ni, and D. Weissman, Immunity (2005) doi: 10.1016/j.immuni.2005.06.008. PMID: 16111635

Current Hours & Holiday Schedule

The Interprofessional Health Sciences Library remains open with continued modifications in place to conform with state guidance on reopening libraries. Please read and abide by our rules below.

Current hours for the IHS Library:

- Monday – Friday: 6:30 am – 9:00pm
- Saturday & Sunday: CLOSED

Holiday Schedule:

The IHS Library will close at 9:00pm on Tuesday, December 22 and reopen at 6:30am on Monday, January 4.

The IHS Library is Reopening!

The Interprofessional Health Sciences Library will reopen on Monday, August 24 at 6:30am, with modifications in place to conform with state guidance on reopening libraries.

Seating in the library has been significantly reduced to ensure physical distancing, and many of the desktop computers have been removed. Study rooms can only have one occupant at a time.

We want our library users to be aware of how we need your help to remain open and not be a source of new infections. Please see our New IHS Library Rules below.

Operating hours for the IHS Library will be limited and subject to change. Our hours will be:

Monday – Friday, 6:30 am – 9pm
CLOSED on Saturdays and Sundays

Even though our library will look and feel a bit different, we are so excited to reopen and get to see you all soon!

Opioid Abuse in the COVID-19 Era

Somewhat lost in the worldwide COVID-19 health crisis is the continued destruction of lives through opioid abuse. Metaphorically speaking, it is as if the COVID-19 tsunami landed on a beach already flooded by the storm of the opioid abuse epidemic. One crisis does not mitigate the effects of the other; indeed, early data point to increasing opioid use, with already unacceptable consequences only looking to get worse.

Perhaps COVID-19’s effects on substance abuse was predictable – the pandemic has impacted people in numerous ways, many independent of actual viral infection. Social distancing requirements result in increased isolation and alienation. Economic turmoil has caused widespread unemployment (or reduced employment), leading many people to experience deep financial stress and anxiety. For those battling past abusive/addictive behaviors, the pandemic is a relapse catalyst – setting in motion a return to highly destructive actions, attitudes, and decisions. Opportunities to speak with healthcare professionals, therapists, faith-based counselors, or other support personnel are severely curtailed. These conditions facilitate the surge in opioid use and abuse being witnessed across the nation.

Opioids

What could possibly be done when two such health crises collide? We can only begin to attempt an answer here:

First, we must remove the stigma associated with opioid abuse. It should be recognized that opioid and related substance abuse/addiction represents a disease state – involving biological, environmental, and behavioral factors. It is not about moral failings, but neural networks; less about poor decision making, and more about limited perceived options. Individuals experiencing addiction deserve respect and an understanding of the toll of dependency; to marginalize them is demeaning and counterproductive.

COVID-19-related social distancing mandates lead to a reduction of diversions available to potential opioid users/abusers. Fewer people are around to witness and help prevent or treat potential overdoses.

In healthcare, there is an emergent consensus on the effectiveness of medication-assisted treatment (MAT), defined by the Substance Abuse and Mental Health Services Administration (a division of the U.S. Department of Health and Human Services) as “the use of FDA-approved medications, in combination with counseling and behavioral therapies, to provide a “whole-patient” approach to the treatment of substance use disorders.”[1] MAT is not replacing one drug with another – this would be an incomplete understanding of the therapy program. The use of buprenorphine, methadone and naltrexone, in combination with counseling and social support/behavioral interventions, have dramatically altered the landscape of opioid use disorder treatment. MAT works – and works well. The problem is the limited number of physicians trained and licensed to administer MAT. Physicians must receive a Drug Addiction Act of 2000 (DATA) waiver (also known as an “X” waiver) to prescribe the requisite drugs and deliver the appropriate behavioral therapies. Physicians may become waivered after 8 hours of didactic training; medical students require 8 hours of specialized training coupled with a clinical experience demonstrating MAT’s use with opioid use disorder patients. Only a small percentage (<10%) of practicing physicians in this country possess the waiver; of those, less than half actually deliver MAT. Some 40% of counties in the U.S. do not have a waivered physician. Tens of thousands of citizens die from opioid use disorder every year – we must increase the number of X waivered physicians and encourage more to practice the therapy.

If there is any silver lining to the COVID-19 crisis, it is the enabling of telemedicine. For those sheltering in place but requiring access to the health system, telemedicine offers a world of new possibilities. Every attempt must be made to promote digital literacy in vulnerable populations to maximize the impact of this technology.

Recognizing the devastation wrought by COVID-19’s impact on opioid abuse disorders, several local and state jurisdictions across the country are trying to help. As per recommendations made by the American Medical Association[2],[3], several changes are afoot. Buprenorphine may now be prescribed to patients by phone or telemedicine encounter. Methadone is being prescribed in amounts that will last almost a month. These lifesaving drugs are being delivered directly to patients in their homes. The process to have prescriptions refilled has also been streamlined – for example, no toxicology or other testing is required. These developments enable care without the risk of exposure to COVID-19 inherent in in-person visits. Finally, naloxone is being recognized as the true overdose wonder drug – and is being far more liberally distributed.

These are incredibly difficult times – with a global viral-based pandemic intersecting with a devastating substance abuse epidemic. However, as with all crises, good ideas, critical reasoning, and evidence-based decision making will chart a course for real change and true improvement. It cannot happen too quickly for all those affected by opioid use disorders.

SRT – July 2020

References:
[1] Medication-Assisted Treatment (MAT). (2020, April 30). Retrieved July 06, 2020, from https://www.samhsa.gov/medication-assisted-treatment

[2] COVID-19 policy recommendations for OUD, pain, harm reduction. (2020, July 2). Retrieved July 06, 2020, from https://www.ama-assn.org/delivering-care/public-health/covid-19-policy-recommendations-oud-pain-harm-reduction

[3] Taking action on opioid use disorder, pain & harm reduction during COVID-19. (2020, July 2). Retrieved July 06, 2020, from https://www.ama-assn.org/delivering-care/opioids/taking-action-opioid-use-disorder-pain-harm-reduction-during-covid-19

Call for Submissions: COVID-19 Oral History Project

To reconnect as a community during the COVID-19 pandemic, SHU University Libraries seek your stories of what this time has been like for you. We hope that sharing these stories with one another will bring us back together in a new way, through sharing our personal experiences of this moment.

HOW TO PARTICIPATE:

Please record a 1-3 minute narrative about your experience, using any video or audio equipment available to you, and submit the file to our e-Repository (Under “Author Corner”: Submit Contribution in the left column. If you don’t have an account, you will need to create one). Please also submit an image that represents your narrative, which will appear next to your recording in the published archive.

Questions to guide your response:

What is your day to day life like? What would you want people the future to know about what life is like for us now?
What has been most challenging about this time? What do you miss about your life before COVID-19? Are there specific places or things on campus that you miss?
Essential is a word we are hearing a lot right now. What does essential mean to you? Who is essential? What are we learning about what is essential?
What is COVID-19 making possible that never existed before? What good do you see coming out of this moment? How can we re-frame this moment as an opportunity?
What is it you want to remember about this time? What have you learned?
After this pandemic ends, will things go back to the way they were? What kinds of changes would you like to see? How will you contribute to rebuilding the world? What will you do differently?

With thanks to the scholars and librarians who came together to create this project: Professors Angela Kariotis Kotsonis, Sharon Ince, Marta Deyrup, Lisa DeLuca, and Alan Delozier, Technical Services Archivist Sheridan Sayles and Assistant Deans Elizabeth Leonard and Sarah Ponichtera.

Information Resources on Coronavirus Disease 2019 (COVID-19)

Update (2.28.2020): We’ve migrated the below information to the Information Resources on Coronavirus Disease 2019 (COVID-19) toolkit. This toolkit will be updated as additional resources and information is published.

The IHS Library recommends consulting the following resources for factual, up-to-date information on Coronavirus Disease 2019 (COVID-19).

Health Agency Information:

Coronavirus Disease 2019 (Centers for Disease Control and Prevention): Contains information about what you should know about the Coronavirus, situation updates, including a list of locations of confirmed cases, and information resources for travelers and healthcare professionals.

Coronavirus disease (COVID-19) outbreak (World Health Organization): Contains rolling updates about the disease outbreak, as well as important myth-busters to stop the spread of false information. You may also wish to take the WHO e-learning module, Emerging respiratory viruses, including COVID-19: methods for detection, prevention, response and control.

Research Resources:

2019-nCoV (PubMed): A preformulated search will bring up the latest research from the National Library of Medicine’s PubMed Database.

Coronavirus Disease 2019 (JAMA): JAMA Network’s updates on coronavirus diagnosis and treatment, along with recent articles.

Coronavirus (Covid-19) (New England Journal of Medicine): A collection of articles and other resources on the Coronavirus (Covid-19) outbreak, including clinical reports, management guidelines, and commentary.

Novel Coronavirus Information Center (Elsevier): Elsevier is providing free health and medical research on COVID-19, which includes access to the Coronavirus Research Repository.

Information for Patients:

Coronavirus Infections (MedlinePlus): MedlinePlus is a service of the National Library of Medicine (NLM), which provides quality, plain-language information for patients.