Oral DMSO Treatment for Lipoidproteinosis: Efficacy, Risks, and Alternative Therapies

11.07.202317.07.2023 by alexxlab

What are the health benefits of oral DMSO treatment for lipoidproteinosis. What are the potential side effects and precautions to consider. How effective is DMSO compared to other treatment options for this rare genetic disorder.

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Understanding Lipoidproteinosis: A Rare Genetic Disorder

Lipoidproteinosis, also known as Urbach-Wiethe disease, is an uncommon autosomal recessive disorder characterized by the deposition of hyaline material in the skin, mucous membranes, and internal organs. This rare condition affects both males and females equally and typically manifests in early childhood.

What are the main clinical features of lipoidproteinosis?

Hoarseness of voice, often present from infancy
Thickening and scarring of the skin and mucous membranes
Beaded papules along the eyelid margins
Waxy, yellow skin lesions
Neurological symptoms in some cases

The chronic and progressive nature of lipoidproteinosis poses significant challenges for patients and healthcare providers alike. While the condition is generally considered benign, it can significantly impact quality of life due to its varied manifestations.

Oral DMSO Treatment: Mechanism of Action and Potential Benefits

Dimethyl sulfoxide (DMSO) is an organosulfur compound with a wide range of biological activities. Its use in lipoidproteinosis treatment stems from its potential anti-inflammatory, antioxidant, and tissue-penetrating properties.

How might DMSO theoretically benefit patients with lipoidproteinosis?

Reduction of hyaline material deposition
Improvement in skin elasticity and texture
Alleviation of mucosal thickening
Potential improvement in voice quality

Despite these theoretical benefits, clinical evidence supporting the efficacy of oral DMSO treatment for lipoidproteinosis remains limited and controversial.

Clinical Evidence: Evaluating the Efficacy of Oral DMSO Treatment

The study by Ozkaya-Bayazit et al. provides valuable insights into the long-term use of oral DMSO in patients with lipoidproteinosis. This case series involved three patients – two sisters and an unrelated man – who were treated with oral DMSO at a dose of 60 mg/kg/day for an average of 3 years.

What were the outcomes of this long-term DMSO treatment?

No beneficial effects observed on skin lesions
No improvement in mucosal manifestations
Persistent hoarseness without amelioration
Disease progression in one patient, including worsening hoarseness and dyspnea

These findings stand in contrast to an earlier report by Wong and Lin, which described a “remarkable response” to oral DMSO treatment in a patient with lipoidproteinosis. This discrepancy highlights the need for larger, controlled studies to establish the true efficacy of DMSO in this rare disorder.

Safety Profile and Potential Side Effects of Oral DMSO Treatment

While the study by Ozkaya-Bayazit et al. did not report significant adverse effects from long-term DMSO use, it’s crucial to consider the potential risks associated with this treatment approach.

What are some known side effects of oral DMSO administration?

Gastrointestinal disturbances (nausea, vomiting, diarrhea)
Skin irritation or rash
Halitosis (bad breath) with a characteristic garlic-like odor
Potential hepatotoxicity with long-term use
Interactions with other medications due to DMSO’s ability to enhance drug absorption

The lack of observed benefits in the reported cases, coupled with these potential risks, raises questions about the overall risk-benefit profile of oral DMSO treatment for lipoidproteinosis.

Alternative Treatment Approaches for Lipoidproteinosis

Given the limited success of oral DMSO treatment, it’s important to explore other therapeutic options for managing lipoidproteinosis. While no curative treatment exists, several approaches have been investigated with varying degrees of success.

What are some alternative treatments that have been explored for lipoidproteinosis?

Retinoids (e.g., acitretin): Shown promise in some case reports
Carbon dioxide laser therapy: For managing localized skin lesions
Dermabrasion: May help improve skin texture
Surgical interventions: For managing specific complications (e.g., vocal cord infiltrates)
Supportive care: Speech therapy, psychological support, etc.

Among these, retinoids have garnered particular interest. A case report by Bakry et al. described successful treatment of two Egyptian patients with lipoidproteinosis using acitretin, suggesting that this approach may be more promising than DMSO for some patients.

Individualizing Treatment: Factors to Consider in Lipoidproteinosis Management

The heterogeneous nature of lipoidproteinosis and the varied responses to different treatments underscore the importance of individualized management strategies.

What factors should be considered when developing a treatment plan for lipoidproteinosis?

Severity and distribution of skin and mucosal lesions
Presence and extent of extracutaneous manifestations
Impact on quality of life (e.g., voice changes, cosmetic concerns)
Patient age and overall health status
Potential risks and benefits of available treatment options
Patient preferences and treatment goals

A multidisciplinary approach involving dermatologists, otolaryngologists, neurologists, and other specialists as needed can help ensure comprehensive care for patients with this complex disorder.

Future Directions: Research Needs and Emerging Therapies

The limited efficacy of current treatments, including oral DMSO, highlights the need for continued research into novel therapeutic approaches for lipoidproteinosis.

What are some promising areas for future research in lipoidproteinosis treatment?

Gene therapy targeting the ECM1 gene mutations responsible for the disorder
Development of targeted small molecule drugs to reduce hyaline material deposition
Exploration of combination therapies to address multiple aspects of the disease
Identification of biomarkers to predict treatment response and monitor disease progression
Large-scale, multicenter clinical trials to evaluate existing and novel therapies

Advances in our understanding of the molecular mechanisms underlying lipoidproteinosis may pave the way for more effective, targeted treatments in the future.

Practical Considerations for Patients and Caregivers

While research continues, patients with lipoidproteinosis and their caregivers must navigate the challenges of living with this rare disorder. Practical strategies can help manage symptoms and improve quality of life.

What are some practical tips for individuals affected by lipoidproteinosis?

Regular moisturization of the skin to improve texture and reduce dryness
Sun protection to minimize UV-induced skin damage
Voice therapy exercises to maintain or improve vocal function
Regular dental check-ups to monitor and manage oral manifestations
Psychological support to address the emotional impact of the condition
Connecting with support groups or patient organizations for shared experiences and resources

Education about the condition and open communication with healthcare providers are crucial for optimal management and coping with lipoidproteinosis.

The Role of Genetic Counseling in Lipoidproteinosis

Given the autosomal recessive inheritance pattern of lipoidproteinosis, genetic counseling plays a vital role for affected individuals and their families. Understanding the genetic basis of the disorder can inform family planning decisions and help identify at-risk relatives.

What are the key aspects of genetic counseling for lipoidproteinosis?

Explanation of the inheritance pattern and recurrence risks
Discussion of available genetic testing options
Prenatal and preimplantation genetic diagnosis considerations
Psychosocial support for individuals and families dealing with the diagnosis
Information about ongoing research and clinical trials

Genetic counseling can empower individuals and families with the knowledge needed to make informed decisions about their health and reproductive choices.

Monitoring and Long-term Management of Lipoidproteinosis

The chronic nature of lipoidproteinosis necessitates ongoing monitoring and management to address evolving symptoms and potential complications. Regular follow-up with a multidisciplinary team is essential for optimal care.

What aspects of lipoidproteinosis require ongoing monitoring?

Skin and mucosal lesions: Regular dermatological assessments
Voice and laryngeal function: Periodic ENT evaluations
Neurological status: Monitoring for seizures or other CNS manifestations
Ophthalmological health: Regular eye exams to detect and manage ocular complications
Psychological well-being: Assessment and support for mental health concerns

Proactive management and early intervention for emerging symptoms can help minimize the impact of lipoidproteinosis on patients’ overall health and quality of life.

The Importance of Patient Registries and Collaborative Research

Given the rarity of lipoidproteinosis, patient registries and collaborative research initiatives are crucial for advancing our understanding of the disorder and developing more effective treatments.

How do patient registries and collaborative research benefit lipoidproteinosis patients?

Facilitate natural history studies to better characterize disease progression
Enable larger-scale clinical trials by pooling patients across multiple centers
Promote standardization of care and development of clinical guidelines
Provide a platform for patient-reported outcomes and quality of life assessments
Foster connections between patients, researchers, and healthcare providers

Participation in registries and research studies offers patients an opportunity to contribute to scientific progress while potentially gaining access to novel therapies and expert care.

Addressing the Psychosocial Impact of Lipoidproteinosis

The visible manifestations and chronic nature of lipoidproteinosis can have significant psychosocial effects on affected individuals. Addressing these aspects is crucial for comprehensive patient care.

What psychosocial challenges may lipoidproteinosis patients face?

Body image concerns due to skin lesions and facial changes
Social anxiety related to voice alterations
Emotional distress from the chronic and progressive nature of the disorder
Challenges in school or work environments due to physical manifestations
Feelings of isolation due to the rarity of the condition

Integrating psychological support, counseling, and patient support groups into the overall management plan can help address these challenges and improve patients’ overall well-being.

Emerging Technologies in Lipoidproteinosis Diagnosis and Management

Advancements in medical technology offer new opportunities for improving the diagnosis, monitoring, and treatment of lipoidproteinosis.

What emerging technologies show promise in lipoidproteinosis care?

Advanced imaging techniques for non-invasive assessment of tissue involvement
Artificial intelligence-assisted analysis of skin lesions and disease progression
Telemedicine platforms for remote monitoring and specialist consultations
Wearable devices for continuous monitoring of voice and skin parameters
3D printing technologies for customized therapeutic devices or prosthetics

While many of these technologies are still in developmental stages, they hold the potential to significantly enhance the care and quality of life for individuals with lipoidproteinosis in the future.

The Role of Patient Advocacy in Advancing Lipoidproteinosis Care

Patient advocacy plays a crucial role in raising awareness, promoting research, and improving care for rare disorders like lipoidproteinosis.

How can patient advocacy efforts benefit the lipoidproteinosis community?

Increase public and professional awareness of the disorder
Advocate for research funding and policy changes to support rare disease research
Facilitate connections between patients, researchers, and healthcare providers
Provide educational resources and support for patients and families
Promote the development of patient-centered outcome measures for clinical trials

Empowering patients and families to become advocates can drive progress in lipoidproteinosis research and care, ultimately improving outcomes for all affected individuals.

[Oral DMSO therapy in 3 patients with lipoidproteinosis. Results of long-term therapy]

Case Reports

. 1997 Jul;48(7):477-81.

doi: 10.1007/s001050050613.

[Article in

German]

E Ozkaya-Bayazit¹, G Ozarmağan, C Baykal, T Uluğ

Affiliations

Affiliation

¹ Dermatologische Abteilung, Medizinischen Fakultät Istanbul der Universität, Istanbul.

PMID:
9333627
DOI:
10.1007/s001050050613

Case Reports

[Article in

German]

E Ozkaya-Bayazit et al.

Hautarzt.

1997 Jul.

. 1997 Jul;48(7):477-81.

doi: 10.1007/s001050050613.

Authors

E Ozkaya-Bayazit¹, G Ozarmağan, C Baykal, T Uluğ

Affiliation

¹ Dermatologische Abteilung, Medizinischen Fakultät Istanbul der Universität, Istanbul.

PMID:
9333627
DOI:
10.1007/s001050050613

Abstract

Lipoid proteinosis is a rare autosomal recessive disorder with a chronic, benign course. There is no generally accepted systemic therapy apart from the experimental oral use of dimethyl sulphoxide (DMSO) and etretinate in two single cases. We treated two sisters and an unrelated man with lipoid proteinosis with longterm oral DMSO (60 mg/kg/d). At the end of an average treatment time of 3 years, DMSO was withdrawn because it produced no beneficial effects with regard to their skin, mucosal lesions or hoarseness. Additionally, one patient showed progression of her disease with worsening hoarseness and onset of dyspnea, requiring surgical removal of vocal cord infiltrates. Three patients with lipoid proteinosis failed to show any beneficial response to long term treatment with DMSO.

Cited by

Two Egyptian cases of lipoid proteinosis successfully treated with acitretin.
Bakry OA, Samaka RM, Houla NS, Basha MA.
Bakry OA, et al.
J Dermatol Case Rep. 2014 Mar 31;8(1):29-34. doi: 10.3315/jdcr.2014.1168. eCollection 2014 Mar 31.
J Dermatol Case Rep. 2014.
PMID: 24748909
Free PMC article.
Cryosurgery (N2O) Application to Remove Lip Lesions of Lipoid Proteinosis Syndrome: A Case Report.
Shirani AM.
Shirani AM.
J Dent Res Dent Clin Dent Prospects. 2008 Spring;2(2):68-70. doi: 10.5681/joddd.2008.014. Epub 2008 Aug 15.
J Dent Res Dent Clin Dent Prospects. 2008.
PMID: 23289062
Free PMC article.
Acitretin treatment for lipoid proteinosis.
Gündüz O, Sahiner N, Atasoy P, Senyücel C.
Gündüz O, et al.
Case Rep Dermatol Med. 2012;2012:324506. doi: 10.1155/2012/324506. Epub 2012 Aug 9.
Case Rep Dermatol Med. 2012.
PMID: 23259080
Free PMC article.

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DMSO (Dimethyl Sulfoxide): Uses, Benefits, Risks, and More

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Medically reviewed by Angelica Balingit, MD — By Jessica DiGiacinto and Joe Bowman — Updated on May 16, 2023

DMSO is a colorless chemical solvent that may have many medical uses but is currently only approved by the FDA to treat interstitial cystitis.

The story of dimethyl sulfoxide (DMSO) is an unusual one. This by-product of the paper making process was discovered in Germany in the late 19th century. It’s a colorless liquid that gained notoriety for its ability to penetrate the skin and other biological membranes.

Scientists discovered that they could use DMSO as a transportation device to pass small molecules through skin in the 1960s. Since then, scientists have researched the potential benefits and risks of using DMSO to treat a variety of conditions. This research is ongoing.

DMSO was approved by the Food and Drug Administration (FDA)to treat interstitial cystitis (a chronic bladder issue) under the brand name RIMSO-50.

The compound has no other approved uses, but it’s been purported to be a treatment for:

arthritis
cancer
chemotherapy side effects
general pain

Because it absorbs easily into the skin, it’s also been studied as a vehicle for administering topical drugs.

In the late 70s, the FDA approved DMSO to help treat interstitial cystitis. It remains the only FDA-approved bladder installation (or bladder wash) for this condition. For individuals living with interstitial cystitis, DMSO has been shown to:

ease pain due to the condition
help relax the bladder
increase bladder capacity

When it comes to off-label uses, DMSO is often employed as an alternative treatment to reduce inflammation and pain.

Because it absorbs easily into the skin, DMSO may be a beneficial alternative to other pain medications. However, further investigation into this area is needed before any conclusions can be drawn.

DMSO has also been touted for its ability to reduce the amount of leakage during chemotherapy administration, but more studies, and real-world usage, need to be done before it can be labeled as a trusted method.

Additionally, there has been some research into DMSO’s benefits when it comes to inhibiting cancer cells. A 2020 study published in the Journal of Medical Discovery found evidence of benefit. However, research is just beginning in this area, so many more studies need to be done before any conclusions can be made.

While many of the reported side effects of taking DMSO are mild, the amount of DMSO someone takes is directly correlated to the severity of the reaction.

One common side effect is the taste of garlic in the mouth and throat.

More severe side effects include:

headache
nausea
vomiting
stomach ache
diarrhea
fever
chills
a lowered heart rate
itching
rash
rough or thickened skin

Risks

Because it’s seen as a more alternative treatment, DMSO is easy to find and buy online. However, buying this product and using it without a healthcare professional’s supervision could increase the likelihood of overuse.

DMSO may also increase the effect of a few medications, which could produce serious reactions in some people. A few medications DMSO may affect include:

sedatives
blood thinners
steroids

DMSO can be administered

topically, via a gel or solution
as a bladder wash, via a catheter (for interstitial cystitis)

As with any alternative treatment, it’s always advised to talk with a doctor before deciding to purchase any product that contains DMSO. Dosage is directly connected to the severity of possible side effects.

Dimethyl sulfoxide (DMSO) is a chemical solvent that is sometimes used to help reduce inflammation and pain, and may also be beneficial in reducing leakage during chemotherapy treatment.

It has been FDA approved to treat only one condition: interstitial cystitis.

Because of possible interactions with other common medications, and lack of definitive research into its benefits, DMSO should not be used without medical supervision.

Last medically reviewed on February 1, 2022

How we reviewed this article:

Healthline has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical associations. We avoid using tertiary references. You can learn more about how we ensure our content is accurate and current by reading our editorial policy.

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Tang H, et al. (2020). DMSO inhibits growth and induces apoptosis through extrinsic pathway in human cancer cells.
https://www.proquest.com/openview/06527232a660b6867effa2ff8f68deed/1?pq-origsite=gscholar&cbl=2050635
Understanding unapproved use of approved drugs “off-label.” (2018).
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urologyhealth.org/urology-a-z/i/interstitial-cystitis

Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available.

Current Version

May 16, 2023

Written By

Jessica DiGiacinto, Joe Bowman

Edited By

Jessica DiGiacinto

Copy Edited By

Delores Smith-Johnson

Feb 1, 2022

Medically Reviewed By

Angelica Balingit, MD

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Medically reviewed by Angelica Balingit, MD — By Jessica DiGiacinto and Joe Bowman — Updated on May 16, 2023

Efficacy of some antiviral agents against COVID-19: in vitro studies

Authors: Xi Wang, Ruiyuan Cao, Huanyu Zhang, Jia Liu, Mingyue Xu, Hengrui Hu, Yufeng Li, Lei Zhao, Wei Li, Xiulian Sun, Xinglou Yang, Zhengli Shi, Fei Deng, Zhihong Hu, Wu Zhong, Manli Wang2020, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease COVID-19 rapidly spread to more than 200 countries, infected more than 1. 5 million people, and caused 92,798 deaths (data as of April 10, 2020). of the year). The World Health Organization (WHO) declared the COVID-19 pandemic on March 11 and called for accelerated development of diagnostic procedures, vaccines and drugs to combat this new disease. In addition to the novel coronavirus infection, influenza viral infections have been a persistent threat to global public health for many years. In the United States only, as estimated by the Centers for Disease Control and Prevention (CDC), during the 2019 winter season-2020, there were at least 39 million cases, 400,000 hospitalizations, and 24,000 influenza deaths (https://www.cdc.gov/flu/weekly/index.htm). Considering that the current circulation of SARS-CoV-2 is accompanied by other influenza viral infections, the study of available and effective drugs for the treatment of both diseases is of great interest.

Indeed, in the early stages of the COVID-19 outbreak, some influenza drugs (eg, oseltamivir) were used to treat patients with COVID-19[12]. We previously reported that favipiravir (T705), an anti-influenza drug approved in Japan and China, showed some efficacy against SARS-CoV-2 in in vitro studies [3]. In addition, umifenovir, an anti-influenza drug with the main antiviral component hemagglutinin (HA), is being used in a clinical trial against COVID-19 (ChiCTR2000029573) and has recently been added to the COVID-19 Diagnosis and Treatment Guidelines (sixth and seventh editions) in China. A recent retrospective study showed that treatment with umifenovir increased the number of recoveries and reduced mortality rates in patients with COVID-19[4]. However, to the best of our knowledge, no systematic analysis of the efficacy of influenza drugs against SARS-CoV-2 has been performed.

In this study, we evaluated the efficacy of six currently available and licensed influenza drugs in the treatment of SARS-CoV-2. These drugs include umifenovir, baloxavir, laninamivir, oseltamivir, peramivir, and zanamivir [5, 6]. M2 inhibitors (amantadine and rimantadine) are not included in this study as they were not recommended by the WHO for the treatment of influenza due to drug resistance. In a first step, the cytotoxicity of compounds in the African green monkey kidney cell line Vero E6 (ATCC-1586) was measured using the standard kit-8 (CCK8) cell scoring method. Cells were then infected with SARS-CoV-2 with a MOI of 0.05 in the presence of test compound or dimethyl sulfoxide (DMSO) control. Dose-response lines were constructed by quantifying the copy number of viral RNA in the infected cell supernatant 48 hours after infection (p. i.). As shown in Figure 1A, umifenovir effectively inhibited viral infection in in vitro studies; The 50% maximum effective concentration (EC 50 ) and 50% cytotoxic concentration (CC 50 ) of umifenovir were 4.11 (3.55-4.73) and 31.79(29.89-33.81) µm, respectively, and the selectivity index (SI = CC50/EC50) is 7.73. Baloxavir partially inhibited SARS-CoV-2 infection (~29%) at a high concentration of 50 μM (Figure 1A). In contrast, laninamivir, oseltamivir, peramivir, and zanamivir did not inhibit SARS-CoV-2 even at the highest drug concentrations (Figure 1A). The antiviral activity of the compounds was also assessed by observing cytopathic effects (CPE) and immunofluorescent staining of infected cells. As shown in Supplementary Figure S1, 48 hours post-infection, only in umifenovir-treated cells but not the other five drugs, viral genome expression and observed cytopathic effect (CPE) to SARS-CoV-2 were significantly reduced. It should be noted that we have also tested some human lung cell lines, such as MRC-5 human embryonic lung fibroblasts and the Calu-3 lung cancer cell line, however, they were not very efficient for SARS-CoV-2 replication and therefore were not used for this. research.

In addition to the influenza virus, umifenovir has been reported to inhibit a wide range of viruses by interfering with several steps in the viral replication cycle [7]. The effect of umifenovir on the stage of SARS-CoV-2 replication was investigated by conducting a preliminary experiment with time-based checkpoints with a frequency of infection (MOI) of 0. 05. Umifenovir was incubated with cells at the beginning of virus entry (Entry), post-entry (Post-entry) and during the entire infection process (Full-time), and the result of the virus was quantified by qRT-PCR. The data obtained showed that umifenovir effectively blocks the virus both at the stage of penetration and immediately after penetration. It has a strong effect on the rate of virus entry (~75% inhibition) with less effect on post-entry events (~55% inhibition) (Figure 1B). In addition, Western blotting (Figure 1C) and immunofluorescence microscopy (Supplementary Figure S2) confirmed that viral genome expression was drastically down-regulated throughout the full-time period (13% of the DMSO group, Figure 1C), and showed a more significant inhibitory effect at the stage of penetration (41%) than at the stage after the beginning of penetration (61%).

Next, a detailed study was carried out on how umifenovir blocks the entry of SARS-CoV-2 into cells. The virus (MOI = 0.05) was allowed to bind to Vero E6 cells at 4°C for 1 hour in the presence of umifenovir (10 μM) or DMSO control. Virus particles bound to the cell (bound virions) and in the supernatant (unbound virions) were analyzed by qRT-PCR. The results showed that treatment with umifenovir resulted in a significant decrease in binding efficiency (67%) compared with the control group (P < 0.05) (Fig. 1d). Accordingly, the proportion of unbound virions increased significantly to 156% of the control group after treatment with umifenovir (P < 0.001) (Figure 1d).

Next, the intracellular movement of the virus was analyzed. As we recently reported, inside infected cells, SARS-CoV-2 underwent vesicle transport, which was first carried out by early endosomes (EEs) and then further transported to endolysosomes (ELs) [8]. Co-localization of virions with endosomes (EEs) or endolysosomes (ELs) was visualized by immunofluorescence microscopy and analyzed statistically (n > 150 cells). As shown in Figure 1e and Supplementary Figure S3, at each time point monitored, there was no significant difference in the number of virions co-localized with EEs when comparing DMSO and umifenovir groups, although as infection progressed (30, 60 and 90 min p. i.), co-localization levels were significantly reduced in both DMSO (24.0%, 5.1% and 3.2%) and umifenovir groups (21.4%, 4.1% and 2.8%), indicating that some virions have already been transported from EEs to the next stage of vesicle transport. In contrast, at 60 min p.i. in the umifenovir group, a slightly higher percentage of virions were transported to ELs (22.4%) than in the DMSO group (18.3%) (P < 0.05) (Figure 1e, f). At 90 min after the start of treatment, significantly fewer virions (~13.5%) were found in the DMSO group, while significantly more virions remained in the umifenovir group (~23.6%), indicating that the drug captured the virus in the DMSO group (P < 0.001) (Fig. 1e, f). Taken together, these results indicated that umifenovir not only interfered with viral attachment, but also with the release of SARS-CoV-2 from intracellular vesicles (ELs).

Among the drugs tested, laninamivir, oseltamivir, peramivir, and zanamivir are the neuraminidase (NA) inhibitors most widely prescribed for the prevention and treatment of influenza. Despite the fact that SARS-CoV-2 does not contain NA analogues, NA inhibitors such as oseltamivir are nevertheless used clinically in the treatment of patients with COVID-19 [1, 2]. Our data indicate that these NA inhibitors were not active against SARS-CoV-2 (Figure 1A), consistent with the conclusion that oseltamivir and zanamivir were ineffective in inhibiting SARS-CoV-2. Baloxavir marboxil is a novel anti-influenza drug that selectively inhibits the endonuclease activity of the viral polymerase responsible for capturing droplet-coated primers from the host mRNA to initiate transcription of the viral mRNA. However, this capillary capture mechanism of endonuclease is not shared by coronaviruses, which encode their own enzymes for the formation of 5′-mRNA structures [10]. This may explain why baloxavir failed to block SARS-CoV-2 infection (Fig. 1a). During this study, Choi et al. also showed that oseltamivir and baloxavirne were able to inhibit SARS-CoV-2 in in vitro studies [11].

Umifenovir, an indole derivative, has been licensed in Russia and China as an antiviral for influenza for several decades. It is a broad-spectrum drug against a wide range of enveloped and non-enveloped viruses. Umifenovir interacts predominantly with aromatic amino acids, and affects several stages of the viral life cycle, either directly affecting viral proteins or virus-associated host factors [7]. For example, in the influenza virus, crystal structures have shown that umifenovir is introduced into the hydrophobic fusion pocket of the HA subunit, thereby preventing the low-temperature conformational change of HA and blocking the fusion process [12]. In hepatitis C virus, umifenovir disrupted both viral attachment and intracellular movement of vesicles [13]. In addition, we found that umifenovir plays a role in the interference between SARS-CoV-2 binding (Fig. 1d) and intracellular vesicle turnover (Fig. 1e, f). Umifenovir can also bind to lipid membranes and change the configuration of cytoplasmic or endosome membranes, which are critical for virus attachment and fusion [7]. Whether umifenovir infects virus and/or cells could be further investigated using a published method [14].

Thus, of the six influenza drugs, only umifenovir effectively suppressed SARS-CoV-2. Functionally, it blocks the spread of the virus, preventing it from attaching and spreading through the ELs. Although the SI of umifenovir is relatively low (SI = 7.73), as with any repurposed drug, its pharmacokinetic profile, including maximum concentration (Cmax), is more important in predicting efficacy. It is believed that if the maximum concentration of Cmax reaches EC 90 , the drug is likely to be effective; while if the Cmax reaches the EC 50 , the drug may be effective in in vivo studies. In humans, a single oral administration of 800 mg umifenovir results in a Cmax of ~4.1 µm [15], and this dosage is effective and safe against various influenza viruses with EC 50 values ranging from 2.5 to 20 µm [7, 16]. Umifenovir also exhibited anti-inflammatory activity, which may increase its efficacy in in vivo studies [16].

Given that the EC 50 (4.11 µm) of umifenovir against SARS-CoV-2 is comparable to or even lower than that of influenza viruses, we therefore suggest that umifenovir is potentially effective in the treatment of patients with COVID-19.

Oral DMSO Treatment for Lipoidproteinosis: Efficacy, Risks, and Alternative Therapies

Understanding Lipoidproteinosis: A Rare Genetic Disorder

Oral DMSO Treatment: Mechanism of Action and Potential Benefits

Clinical Evidence: Evaluating the Efficacy of Oral DMSO Treatment

Safety Profile and Potential Side Effects of Oral DMSO Treatment

Alternative Treatment Approaches for Lipoidproteinosis

Individualizing Treatment: Factors to Consider in Lipoidproteinosis Management

Future Directions: Research Needs and Emerging Therapies

Practical Considerations for Patients and Caregivers

The Role of Genetic Counseling in Lipoidproteinosis

Monitoring and Long-term Management of Lipoidproteinosis

The Importance of Patient Registries and Collaborative Research

Addressing the Psychosocial Impact of Lipoidproteinosis

Emerging Technologies in Lipoidproteinosis Diagnosis and Management

The Role of Patient Advocacy in Advancing Lipoidproteinosis Care

[Oral DMSO therapy in 3 patients with lipoidproteinosis. Results of long-term therapy]

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