At Model Medicines, we open our ID Week campaign with this virus not only because of its recent notoriety, but because it embodies the core thesis of our work. 

Therapeutic readiness must begin before a virus becomes headline news. 

MDL-001, our lead compound, is designed for precisely this task. But before we look forward, we begin by looking back.

A Brief History of Human Coronaviruses

In 1964, virologist June Almeida in the U.K. used electron microscopy to visualize a novel cold virus (B814) with a halo-like crown, inspiring the name “coronavirus”. Around the same time, Dr. David Tyrrell’s team at the Common Cold Unit isolated other coronaviruses. (229E and OC43) from respiratory infections. Tyrell collaborated with Almeida to compare these viruses, confirming via electron microscopy that B814 and 229E shared distinct morphological features

For decades, these “endemic” coronaviruses (229E, OC43, NL63, HKU1) were known to cause mostly mild colds, contributing to ~15–30% of common colds.

This changed dramatically in the 21st century. The growing interconnectedness of the world, coupled with increased human-animal interaction, created fertile ground for coronaviruses to make the perilous leap from animal hosts to humans, ushering in a new era of viral threats. This zoonotic spillover led directly to the emergence of highly pathogenic strains like SARS-CoV, MERS-CoV, and SARS-CoV-2, fundamentally altering the global perception of coronaviruses and underscoring their potent pandemic potential.

• SARS-CoV-1 (SARS): In late 2002, a novel severe acute respiratory syndrome coronavirus emerged in Guangdong, China, causing a global outbreak in 2003 with ~8,098 cases and 774 deaths (~9.6% fatality). The 2003 SARS outbreak was solved by a global network of scientists. Notably, Dr. Carlo Urbani (WHO) first alerted the world to SARS, and labs in Hong Kong (led by Prof. Malik Peiris), the U.S. CDC, and Canada isolated and sequenced the virus. SARS-CoV-1 was linked to civet cats as the intermediate host and likely had bat origins. International collaboration led by the WHO and laboratories worldwide identified the SARS pathogen as a coronavirus by March 2003. The outbreak was contained by July 2003 through public health measures, but the episode marked the first clear recognition of coronaviruses as zoonotic threats with pandemic potential.
  
  

• MERS-CoV (MERS): First reported in 2012 by Dr. Ali Mohamed Zaki in Saudi Arabia, and later sequenced by Ron Fouchier's team at Erasmus MC, Middle East Respiratory Syndrome coronavirus has caused sporadic outbreaks with a very high case fatality (~35%). As of 2025, roughly 2,638 cases and 957 deaths have been reported across 27 countries since 2012. MERS remains a significant public health concern due to its high fatality rate and potential for wider outbreaks, with no specific antiviral treatments or vaccines currently available, leaving supportive care as the only option. Major international gatherings, such as the upcoming World Cup and Expo 2030 in Saudi Arabia and across the region, underscore ongoing concerns about MERS-CoV resurgence and coronavirus spillover in high-density settings with increased human-animal interface and global travel.
  
  

• SARS-CoV-2 (COVID-19): Discovered in Wuhan, China, in late 2019, this novel coronavirus sparked the COVID-19 pandemic. Chinese scientists, including Dr. Li Wenliang, the whistleblower who warned colleagues of a new “SARS-like” virus, and Dr. Yong-Zhen Zhang, who sequenced and published the viral genome in January 2020, confirming it as a SARS-related coronavirus. The virus spread globally, and by March 2020, the WHO declared a pandemic. Its case fatality rate has varied by geography, age group, and variant, generally falling below 2%, but the total burden has far surpassed its predecessors. COVID-19 has since infected hundreds of millions worldwide. By early 2023, over 755 million confirmed cases and 6.8 million deaths had been recorded globally. In the U.S. alone, 100+ million cases have been reported to date, and COVID-19 remains an endemic but serious illness. The pandemic accelerated interest in coronavirus biology and therapeutics, though many of the structural gaps in antiviral readiness remain.

Therapeutic Landscape and Standard of Care

Modern coronavirus therapeutics focus on two fronts: antiviral drugs that target the virus itself, and immunomodulators that treat the inflammatory complications of severe COVID-19. 

The standard of care has evolved quickly since 2020, and currently includes:  

• Remdesivir (Veklury) – Intravenous antiviral (RNA polymerase inhibitor). Remdesivir is a nucleotide analog developed initially for Ebola and became the first FDA-approved COVID-19 treatment. It inhibits the viral RNA-dependent RNA polymerase, halting viral replication. It was the first antiviral approved for COVID-19. In hospitalized patients, a 5-day IV course of remdesivir shortened recovery time from 15 to 10 days on average. There was a trend toward lower mortality (11.4% vs 15.2% by day 29 in the ACTT-1 trial) but not statistically significant. Remdesivir is standard care for hospitalized cases and was later also used off-label as a three-day outpatient IV therapy (shown to reduce hospitalization risk by ~87% in high-risk patients in a clinical trial). It is generally well-tolerated; the main limitation is the need for IV administration.
  
  Origins of Remdesivir (Gilead Sciences): Remdesivir (GS-5734) was invented by Gilead Sciences, building on a decade of antiviral research. Originally created and developed in 2009, to treat hepatitis C and respiratory syncytial virus (RSV), it was then repurposed and studied as a potential treatment for Ebola virus disease and Marburg virus infections. A team led by Dr. Tomas Cihlar at Gilead (one of the pupils of the prominent scientist Antonín Holý, who developed the antiviral drugs used in the treatment of HIV and AIDS, which we will highlight in later weeks) as well as Richard L. Mackman, John P. Bilello, Kai-Chung Cheng, with external academic contributors Richard Whitley, Mark Denison, and Richard Plemper in collaboration with U.S. CDC scientists, discovered remdesivir’s broad activity in 2014–2016. It was in trials for Ebola in 2018 (it showed some effect, but wasn’t the top Ebola therapy). When COVID-19 hit, Gilead rapidly deployed remdesivir in trials (the NIH-run ACTT-1). By May 2020, remdesivir became the first antiviral with an FDA Emergency Use Authorization for COVID-19. 
  
  

• Nirmatrelvir–Ritonavir (Paxlovid) – Oral antiviral (protease inhibitor). Paxlovid is a combination of nirmatrelvir (which inhibits the SARS-CoV-2 3CL protease, an enzyme the virus needs to replicate) and ritonavir (which boosts nirmatrelvir levels, a CYP3A inhibitor). In high-risk outpatients, Paxlovid reduced the risk of hospitalization or death by ~89% in clinical trials. It is most effective when given within 5 days of symptom onset. Paxlovid is now the first-line therapy for non-hospitalized COVID-19 patients at risk of severe disease, thanks to its strong efficacy. Common considerations include potential drug–drug interactions due to ritonavir and concerns around rebound viral replication.

  
  Origins of Paxlovid (Pfizer): Paxlovid originated from Pfizer’s antiviral research programs. Pfizer had been working on 3CL protease inhibitors since the SARS outbreak in 2003, and when COVID-19 struck, their medicinal chemistry team (led by Pfizer scientists in California and the U.K.) rapidly optimized a lead compound (PF-07321332, now nirmatrelvir). The team included Mikael Dolsten, John Ludwig, Andrew McKillop, Claire Moylan, Jay Purdy, Britton Boras, as well as Weili Yu, Mahesh K. Krishnan, Matt Weekly, Ravi M. Shanker, Pankaj Doshi, John A. Ragan, Robert A. Greene, Brett Gampper, and Stéphane Caron
  
  

• Molnupiravir (Lagevrio) – Oral antiviral (nucleoside analog mutagen). Molnupiravir induces lethal mutations in the virus. In the Phase 3 MOVe-OUT trial of unvaccinated high-risk adults, it reduced hospitalization/death risk from 9.7% to 6.8% (a ~30% relative reduction). This efficacy (30%–48% in different analyses) is markedly lower than Paxlovid’s. Molnupiravir is authorized as an alternative for patients who cannot take other antivirals, but it is considered less effective. Its 5-day oral regimen is easy to administer, but some experts have noted theoretical risks; it works by inducing mutations, raising concerns about the potential to cause mutations in human cells.

  
  Origins of Molnupiravir (Emory University → Merck/Ridgeback): Molnupiravir originated from academic research at Drug Innovations at Emory (DRIVE), where it was known as EIDD-2801. Emory scientists (including Dr. George Painter, Dennis Liotta, David Perryman, Todd Sherer, David S. Stephens, and Deborah Watkins Bruner) were investigating it against equine encephalitis viruses (EEVs) and as a broad antiviral against Ebola, chikungunya, and influenza. In 2019, the National Institute of Allergy and Infectious Diseases (NIAID) approved moving molnupiravir into Phase I clinical trials for influenza. In 2020, Ridgeback Biotherapeutics, a small biotech led by Wendy Holman and Wayne Holman, licensed it, and then Merck partnered to develop it. Merck’s team of Daria Hazuda, Roy Baynes, Eliav Barr, Jay Grobler, and Dean Y. Li conducted the large MOVe-OUT trial. Molnupiravir obtained FDA emergency authorization in December 2021 as the first oral antiviral to do so, shortly before Paxlovid’s EUA. It was a notable academia-to-industry success story, showing how a compound from a university lab quickly went through development with pharma support.
  
  

• Dexamethasone – Corticosteroid immunosuppressant. In hospitalized patients needing supplemental oxygen, dexamethasone (6 mg daily) was the first therapy shown to improve survival in COVID-19. The UK’s RECOVERY trial in 2020 found dexamethasone reduced 28-day mortality by one-third in patients on ventilators and by one-fifth in those on oxygen support. It works by dampening the hyperinflammatory “cytokine storm” that can damage organs in severe COVID-19. Dexamethasone is now a standard of care for hospitalized severe cases, given its clear benefit in reducing deaths. By contrast, it showed no benefit and possible harm in patients not requiring oxygen, so its use is limited to moderate-to-severe illness.

  
  Origins of Dexamethasone (RECOVERY Trial/Oxford University): Dexamethasone is a cheap, generic steroid discovered in 1957 by Philip Showalter Hench, but its repurposing for COVID-19 was led by academics. In March 2020, Professors Peter Horby and Martin Landray at the University of Oxford included dexamethasone in the RECOVERY trial. By June 2020, they found a significant mortality reduction. The UK government and healthcare systems worldwide swiftly adopted dexamethasone for severe cases, making it a first example of an effective COVID-19 drug arising from a publicly funded clinical trial.  
  
  

• IL-6 Inhibitors (Tocilizumab) – Monoclonal antibody immunomodulator. Tocilizumab (an antibody against the IL-6 receptor) is used for critically ill, hospitalized patients with escalating inflammation. In trials (RECOVERY, REMAP-CAP), tocilizumab added to dexamethasone further improved survival and shortened time to recovery in severe cases. It helps by blocking a key inflammatory cytokine (IL-6). Guidelines recommend tocilizumab (or baricitinib, a JAK inhibitor) for certain ICU-level patients to reduce mortality. 

  
  Origins of Tocilizumab (Chugai/Roche): Tocilizumab was developed by Chugai Pharmaceutical, a Japanese company, and later co-developed and commercialized globally by Roche. Researchers at Chugai began investigating IL-6 as a therapeutic target in the 1990s, leading to the development of tocilizumab (originally known as MRA) as an antibody against the IL-6 receptor. It was initially approved for rheumatoid arthritis and other inflammatory conditions. During the COVID-19 pandemic, it was rapidly repurposed and studied in several large clinical trials (such as RECOVERY and REMAP-CAP) due to its immunomodulatory effects and ability to counteract the severe inflammatory response (cytokine storm) seen in critical COVID-19 cases.
  
  

• Baricitinib (Olumiant) – JAK inhibitor immunomodulator. Baricitinib, an oral Janus kinase (JAK) inhibitor, is used for hospitalized COVID-19 patients with progressive disease, often in combination with remdesivir and/or dexamethasone. It works by blocking signaling pathways involved in inflammation (JAK1 and JAK2), thereby reducing the hyperinflammatory response seen in severe COVID-19. Studies, including the ACTT-2 trial, showed that baricitinib, when added to remdesivir, improved recovery time and clinical outcomes compared to remdesivir alone, particularly in those requiring supplemental oxygen. Baricitinib offers an oral alternative to tocilizumab for patients with severe COVID-19 needing immunomodulation.
  
  

  Origins of Baricitinib (Incyte/Eli Lilly): Baricitinib was developed by Incyte and licensed to Eli Lilly and Company. Incyte, a biopharmaceutical company, discovered baricitinib as part of its research into JAK inhibitors for inflammatory and autoimmune diseases. Lilly partnered with Incyte in 2009 for the development and commercialization of baricitinib. It was initially approved for rheumatoid arthritis and later repurposed for COVID-19 after early studies suggested it could reduce inflammation and improve outcomes in severe cases.  

Standard Treatment Regimens

For mild-to-moderate COVID-19 in an outpatient at-risk patient, an oral antiviral (Paxlovid is the first choice; molnupiravir if Paxlovid is contraindicated) is the standard approach to prevent progression. 

For hospitalized patients, remdesivir is often given, especially if within 7–10 days of symptom onset, along with dexamethasone for those requiring oxygen. 

In ICU patients with cytokine storm, dexamethasone plus tocilizumab or baricitinib is recommended to improve outcomes. Supportive care, including oxygen therapy, ventilation as needed, and anticoagulation to prevent clots, remains a cornerstone. 

Vaccination, though not a therapeutic, is part of the standard of care for prevention and indirectly reduces the patient burden.

Emerging and Pipeline Therapeutics

The fight against coronavirus diseases is far from over, and numerous companies and research groups are developing next-generation treatments. Here, we provide a competitive analysis of notable emerging or pipeline therapeutics that could complement or compete with the current standard of care:

• Shionogi’s Ensitrelvir (Xocova) and S-892216: A novel oral 3CL protease inhibitor from Japan’s Shionogi team (Isao Teshirogi, John Keller, Hirofumi Sawa, Akihiko Sato, Takeki Uehara, Hiroki Sakaguchi, Takao Sanaki, Takuhiro Sonoyama, Genki Ichihashi, Takahiro Kawajiri, Masaya Yamato, Jens Lundgren) approved in Japan in late 2022 for COVID-19. Ensitrelvir is similar in mechanism to Paxlovid’s nirmatrelvir but does not require ritonavir boosting due to its longer half-life. Phase 3 trials (SCORPIO-HR) in mostly vaccinated patients showed ensitrelvir significantly accelerated clearance of the virus and improved some symptoms, though it did not significantly shorten overall symptom duration in the total population. Importantly, a subgroup suggested it may reduce the risk of long COVID symptoms. Japan has made ensitrelvir available domestically, and Shionogi is seeking approvals elsewhere. A U.S. Phase 3 is ongoing. Ensitrelvir’s competitive advantage could be its once-daily dosing without ritonavir, making it a convenient alternative to Paxlovid. However, it will need to demonstrate non-inferiority to Paxlovid in preventing hospitalization in high-risk groups to gain global uptake. If it does, it could capture market share, especially for patients who cannot take Paxlovid due to drug interactions. S-892216, an investigational second-generation 3CL protease inhibitor, is being developed both as a long-acting injectable and as an oral drug, intended for prophylaxis and treatment of SARS-CoV-2 infection, respectively.
  
  

• Gilead’s Obeldesivir (Oral Remdesivir Analog): Gilead is advancing an oral prodrug version of remdesivir, named obeldesivir (GS-5245). It targets the same viral polymerase as remdesivir and, once metabolized, works similarly. Obeldesivir is in Phase 2 trials. If successful, it could offer Paxlovid-like convenience with a different mechanism. Being from Gilead, it might benefit from remdesivir’s brand as a proven antiviral, and potentially it could be used in combination with remdesivir for severe cases or with other oral treatments to enhance potency. Gilead has noted the need for oral options and is investing in this candidate to maintain a presence in COVID therapeutics. A potent oral polymerase inhibitor would be a strong competitor to Paxlovid, and also an easy add-on to existing therapy targeting a different viral enzyme.
  
  

• Ibuzatrelvir (PF-07321332 analog): Pfizer’s next-generation Mpro inhibitor under development as a potential follow-up or complement to Paxlovid is currently in phase 3. 
  
  

• Atilotrelvir (GST-HG171), developed by Fujian Akeylink Biotechnology, is an oral Mpro inhibitor currently in phase 3. The compound is part of China's broader push for domestically developed COVID-19 therapeutics.
  
  

These candidates reflect continued interest in protease inhibition as a viable therapeutic axis, though they remain focused on SARS-CoV-2 rather than pan-coronavirus breadth. Their advancement will inform combination therapy design and resistance landscape evolution in the years ahead. For a full list of new pipeline therapeutics, C&EN compiles the latest.

Epidemiology and Patient Population: Global and U.S. Impact

The four endemic human coronaviruses (229E, OC43, NL63, HKU1) are ubiquitous. These viruses circulate seasonally worldwide, but because they’re mild, they are not well-tracked – estimated to cause perhaps 15–30% of upper respiratory tract infections each year. This translates to billions of infections globally over time, though mild ones.

• SARS-CoV-1 (2003 SARS) was contained and no longer circulates in humans. It was a high-profile outbreak, but it is not an ongoing patient population (only survivors with any long-term issues remain, which is a small number).
  
  

• MERS-CoV has caused about 2,600+ cases from 2012–2023, primarily in the Middle East, notably Saudi Arabia. It still sporadically infects people from camels or in hospital clusters. In an average year, only a handful of MERS cases occur (e.g., 2021 saw ~16 cases globally). However, a large outbreak could occur if transmission increases. MERS is a rare disease, but with extremely high mortality when it does strike (~33%), which keeps it on the WHO’s priority pathogen list.
  
  

• SARS-CoV-2 COVID-19 has infected an enormous number of people worldwide in the past three years. As of early 2023, over 755 million confirmed cases had been documented globally, along with 6.8 million reported deaths. The true infection count is likely higher, potentially billions, given asymptomatic cases and limited testing in many regions. COVID-19’s endemic phase still yields a very large patient population – on the order of 10+ million symptomatic cases per year in the U.S. and hundreds of millions globally. Endemic human coronaviruses cause countless mild infections (not a market for treatment except perhaps in rare severe pediatric cases), while MERS remains a lurking threat with a small patient count but high urgency per case. This epidemiological context translates into a sustained demand for coronavirus therapeutics, especially as the world aims to reduce the health burden of COVID-19 for vulnerable populations.

Market Size and 2024 Sales of Leading Coronavirus Therapeutics

The COVID-19 therapeutics market surged during the pandemic and is now entering a new phase. The World Health Organization (WHO) announced in May 2023 that COVID-19 was no longer a global health emergency. Investor interest remains high due to the sizable revenue generated by these drugs and the potential for future sales, including from endemic COVID-19 management, seasonal surges, and stockpiling for pandemics. 

Veklury/remdesivir (Gilead): Remdesivir has been a steady hospital antiviral. Even with fewer hospitalizations, there is a baseline demand for remdesivir. 

Paxlovid/nirmatrelvir/ritonavir (Pfizer): Kevin Marcaida, pharma analyst at GlobalData, forecasts Paxlovid to generate $34 billion in sales from 2023 to 2029, indicating an expected steady market as COVID-19 becomes an annual endemic disease.

Lagevrio/molnupiravir (Merck): Molnupiravir had significant, if short-lived, sales and demonstrated that even a moderately effective drug can yield multi-billion dollar revenue when distributed at scale during a health emergency.

By 2024, with much of the population vaccinated or post-infection, the acute COVID-19 treatment market has contracted from pandemic peaks, but remains significant. The global antiviral market for the three leading products (Paxlovid, Veklury, and Lagevrio) totaled an estimated $8.4 billion in 2024 (Paxlovid ~$5.7B, Veklury ~$1.8B, Lagevrio ~$1.0B). New demand increasingly comes from countries that had limited access in 2021–22 but are now procuring antivirals, creating new growth opportunities in Asia, Latin America, and other emerging regions.

Pandemic preparedness initiatives could lead to advance purchase contracts for broad coronavirus therapeutics, similar to how governments signed advance vaccine deals. The global addressable market thus includes not just ongoing medical needs, but also strategic stockpiling.

Gaps in the Standard of Care and Areas for Improvement: The Unmet Need Remains

Even as vaccine uptake and viral evolution shift SARS-CoV-2 into endemic circulation, the demand for effective outpatient antivirals remains high. Millions continue to experience symptomatic infections, especially in immunocompromised populations, with persistent risks of hospitalization, long COVID, and viral rebound.

• Resistance and Variant Escape: SARS-CoV-2’s rapid evolution poses a constant threat to therapeutics. Monoclonal antibodies can be rendered obsolete by a few mutations on the viral spike. Small-molecule antivirals like Paxlovid could also face resistance; reports have noted viral protease mutations in some patients after Paxlovid therapy. 

  
  

  Need: Broadly active therapies that remain effective against current and future variants or even new coronavirus species are needed. 
  
  

• Broad-Spectrum Antivirals: The current antivirals are mostly specific to SARS-CoV-2. Remdesivir and molnupiravir have broad activity against RNA viruses in vitro, but in practice, they were only approved for COVID-19. The 2003 SARS and 2012 MERS outbreaks were small compared to COVID-19, but had much higher mortality. If a SARS or MERS-like virus re-emerged, we would largely rely on the same supportive care and repurpose COVID drugs, hoping they work. 

  
  Need: We lack a pan-coronavirus drug that could be stockpiled for the next coronavirus outbreak (whether another SARS-like virus or MERS). Developing antivirals that target conserved coronavirus enzymes (like polymerase or protease regions common across coronaviruses) is an area for improvement. Such a drug could act as a “one drug, many viruses” solution to future-proof against novel coronaviruses.
  
  

• Treatment Window and Delivery: Current antivirals are most effective when given very early - within 3–5 days of symptoms. This can be challenging, as patients may seek care too late. A gap exists for therapies that can help later-stage disease. Also, the route of administration is an issue: remdesivir requires IV infusion, limiting its outpatient use. 

  
  Need: There is a need for pre-exposure prophylaxis with more convenient oral or inhaled antiviral formulations. 
  
  

• Drug Interactions and Contraindications: Paxlovid’s ritonavir component interacts with many common medications due to CYP3A inhibition, meaning some patients (e.g., those on certain antiarrhythmics or immunosuppressants) cannot safely take it. There is a gap for an equally effective oral antiviral that doesn’t have these interactions. Likewise, molnupiravir is not recommended in pregnancy due to potential risks. 

  
  Need: Future antivirals with better safety in vulnerable populations (pregnant women, severe renal or liver disease patients, etc.) would improve care inclusivity.
  
  

• Long COVID and Prevention of Sequelae: Another gap is treatments to prevent or treat long COVID (post-acute sequelae). Antivirals given during acute infection might lower long COVID risk by reducing initial damage, but dedicated strategies are lacking.  

  
  Need: Therapies that mitigate long-term effects is needed.

  
  

• MERS and Other Coronavirus Diseases: Outside of COVID-19, for MERS there is still no approved therapeutic. Treatments used have been experimental. The case numbers are too low for big trials, but the ~35% mortality demands a plan

  
  Need: A pan-coronavirus antiviral or monoclonal that could be deployed for MERS outbreaks and likewise for any SARS-CoV-3 that might emerge.

While the current standard of care significantly reduces COVID-19 mortality, it can be fragile in the face of viral evolution and is not accessible to all patients or all coronavirus diseases. There is a strong rationale for investing in next-generation therapeutics that are broader, easier to administer, and effective in later disease stages or other coronavirus infections. Filling these gaps would not only improve outcomes for individual patients but also strengthen global preparedness for future coronavirus outbreaks.